High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway

Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (H...
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Autor*in:	Sudhir Pandey [verfasserIn] Corina T. Madreiter-Sokolowski [verfasserIn] Supachoke Mangmool [verfasserIn] Warisara Parichatikanond [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	high glucose endothelin-1 ET ET mTOR mitochondrial dysfunction

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 22, p 13816
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:22, p 13816

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms232213816

Katalog-ID:	DOAJ083666370

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520			\|a Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ET<sub<A</sub<-R/ET<sub<B</sub<-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ET<sub<A</sub<-R alone by ambrisentan or ET<sub<A</sub<-R/ET<sub<B</sub<-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.
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callnumber-first	Q - Science
author	Sudhir Pandey
spellingShingle	Sudhir Pandey misc QH301-705.5 misc QD1-999 misc high glucose misc endothelin-1 misc ET<sub<A</sub<-R misc ET<sub<B</sub<-R misc mTOR misc mitochondrial dysfunction misc Biology (General) misc Chemistry High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway
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topic_title	QH301-705.5 QD1-999 High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway high glucose endothelin-1 ET<sub<A</sub<-R ET<sub<B</sub<-R mTOR mitochondrial dysfunction
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title	High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway
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title_sort	high glucose-induced cardiomyocyte damage involves interplay between endothelin et-1/et<sub<a</sub</et<sub<b</sub< receptor and mtor pathway
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title_auth	High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway
abstract	Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ET<sub<A</sub<-R/ET<sub<B</sub<-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ET<sub<A</sub<-R alone by ambrisentan or ET<sub<A</sub<-R/ET<sub<B</sub<-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.
abstractGer	Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ET<sub<A</sub<-R/ET<sub<B</sub<-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ET<sub<A</sub<-R alone by ambrisentan or ET<sub<A</sub<-R/ET<sub<B</sub<-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.
abstract_unstemmed	Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ET<sub<A</sub<-R/ET<sub<B</sub<-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ET<sub<A</sub<-R alone by ambrisentan or ET<sub<A</sub<-R/ET<sub<B</sub<-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.
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title_short	High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway
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Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ET<sub<A</sub<-R/ET<sub<B</sub<-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ET<sub<A</sub<-R alone by ambrisentan or ET<sub<A</sub<-R/ET<sub<B</sub<-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. 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High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ET<sub<A</sub</ET<sub<B</sub< Receptor and mTOR Pathway

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