Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease

Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Gjumrakch Aliev [verfasserIn] George E. Barreto [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA

Übergeordnetes Werk:	In: Frontiers in Cellular Neuroscience - Frontiers Media S.A., 2008, 9(2015)
Übergeordnetes Werk:	volume:9 ; year:2015

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/conf.fncel.2015.35.00015

Katalog-ID:	DOAJ037111515

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520			\|a Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.
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allfields	10.3389/conf.fncel.2015.35.00015 doi (DE-627)DOAJ037111515 (DE-599)DOAJ584ac04ab25d4a3f8942b2ed325b0c82 DE-627 ger DE-627 rakwb eng RC321-571 Gjumrakch Aliev verfasserin aut Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA Neurosciences. Biological psychiatry. Neuropsychiatry George E. Barreto verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:9 year:2015 https://doi.org/10.3389/conf.fncel.2015.35.00015 kostenfrei https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 kostenfrei http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
spelling	10.3389/conf.fncel.2015.35.00015 doi (DE-627)DOAJ037111515 (DE-599)DOAJ584ac04ab25d4a3f8942b2ed325b0c82 DE-627 ger DE-627 rakwb eng RC321-571 Gjumrakch Aliev verfasserin aut Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA Neurosciences. Biological psychiatry. Neuropsychiatry George E. Barreto verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:9 year:2015 https://doi.org/10.3389/conf.fncel.2015.35.00015 kostenfrei https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 kostenfrei http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfields_unstemmed	10.3389/conf.fncel.2015.35.00015 doi (DE-627)DOAJ037111515 (DE-599)DOAJ584ac04ab25d4a3f8942b2ed325b0c82 DE-627 ger DE-627 rakwb eng RC321-571 Gjumrakch Aliev verfasserin aut Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA Neurosciences. Biological psychiatry. Neuropsychiatry George E. Barreto verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:9 year:2015 https://doi.org/10.3389/conf.fncel.2015.35.00015 kostenfrei https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 kostenfrei http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfieldsGer	10.3389/conf.fncel.2015.35.00015 doi (DE-627)DOAJ037111515 (DE-599)DOAJ584ac04ab25d4a3f8942b2ed325b0c82 DE-627 ger DE-627 rakwb eng RC321-571 Gjumrakch Aliev verfasserin aut Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA Neurosciences. Biological psychiatry. Neuropsychiatry George E. Barreto verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:9 year:2015 https://doi.org/10.3389/conf.fncel.2015.35.00015 kostenfrei https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 kostenfrei http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfieldsSound	10.3389/conf.fncel.2015.35.00015 doi (DE-627)DOAJ037111515 (DE-599)DOAJ584ac04ab25d4a3f8942b2ed325b0c82 DE-627 ger DE-627 rakwb eng RC321-571 Gjumrakch Aliev verfasserin aut Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases. Alzheimer Disease Nitric Oxide Oxidative Stress Cancer mtDNA Neurosciences. Biological psychiatry. Neuropsychiatry George E. Barreto verfasserin aut In Frontiers in Cellular Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826414 (DE-600)2452963-1 16625102 nnns volume:9 year:2015 https://doi.org/10.3389/conf.fncel.2015.35.00015 kostenfrei https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 kostenfrei http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full kostenfrei https://doaj.org/toc/1662-5102 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
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title_auth	Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease
abstract	Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.
abstractGer	Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.
abstract_unstemmed	Oxidative stress initiates mitochondrial DNA overproliferation and/or deletion of the organ and/or tissues, especially the mitochondrial energy demands, have been implicated in the pathogenesis of several diseases, including Alzheimer disease (AD), tumor growth, and metastasis. The present study has determined if an intimate, i.e. causal, relationship between oxidative stress and mitochondrial damage and/or vascular lesions occurs before the development of human AD, in animal models that mimic human neurodegenerative diseases and human colorectal carcinoid cancer or primary malignant brain cancer. In situ hybridization and ultrastructural analysis of the mitochondria (mitochondria with electron dense matrix, mitochondrial-derived lysosomes) showed that mitochondria with the abnormal structures and lipofuscin appear to be features of hippocampal damaged neurons in human AD, aged Tg (+) mice, 2 and 3 vessel occlusion model of the brain hypoperfusion, and malignant primary and metastatic cancer. The abnormal mitochondria appeared to be a permanent feature in all cellular compartments; in situ hybridization analysis with mouse and human mtDNA probes found a large amount of deleted mtDNA in human AD and in all models that mimic human AD (mice, rats etc.) hippocampus and cancer tissues compared to aged controls. The majority of these mtDNA deletions were found in mitochondrial-derived lysosomes in regions closely associated with lipofuscin and/or tumor growth regions. In situ hybridization with a chimeric cDNA probe for the 5kb common deletion indicated that the 5kb mtDNA is increased at least 3 and 4 fold respectively in AD and malignant tumor cases as compared to controls. Only hippocampal and cortical vulnerable neurons as well as malignant cancer tissues showed immunopositive staining for RNA oxidation markers visualized by using 8-OHG-staining, NOSs, and all oxidative stress markers. The mitochondrial DNA overproliferation and deletion detected by using cytological techniques suggests that successful dysregulation of the cell cycle is also the hallmark of neoplasm; early mitochondrial dependent cell-cycle pathophysiology in AD may recruit oncogenic signal transduction mechanisms and hence, can be viewed as an abortive neoplastic transformation. The common features on the mitochondrial abnormality were seen on the brain during tumorigenesis and AD indicating that mitochondrial DNA overproliferation and/or deletion are the key initiating factors for development, maturation, and progression of neurodegeneration as well as tumor growth and/or metastases. Materials presented in this work indicate that the Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We theorize that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Moreover, our study also demonstrates a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.
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title_short	Nitric Oxide-Dependent Oxidative Stress Induced Mitochondrial DNA Overproliferation and Deletion in the Context of Cancer and Alzheimer Disease
url	https://doi.org/10.3389/conf.fncel.2015.35.00015 https://doaj.org/article/584ac04ab25d4a3f8942b2ed325b0c82 http://journal.frontiersin.org/Journal/10.3389/conf.fncel.2015.35.00015/full https://doaj.org/toc/1662-5102
remote_bool	true
author2	George E. Barreto
author2Str	George E. Barreto
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doi_str	10.3389/conf.fncel.2015.35.00015
callnumber-a	RC321-571
up_date	2024-07-03T23:58:11.577Z
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