A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms
Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Cuadrado-Berrocal, Irene [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
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| Schlagwörter: |
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| Umfang: |
12 |
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| Übergeordnetes Werk: |
Enthalten in: Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement - Chen, Zhuo ELSEVIER, 2023, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:93 ; year:2015 ; number:4 ; day:15 ; month:02 ; pages:428-439 ; extent:12 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.bcp.2014.12.011 |
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ELV03488565X |
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| 245 | 1 | 0 | |a A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms |
| 264 | 1 | |c 2015transfer abstract | |
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| 520 | |a Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. | ||
| 520 | |a Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. | ||
| 650 | 7 | |a Heart |2 Elsevier | |
| 650 | 7 | |a Ischemia/reperfusion injury |2 Elsevier | |
| 650 | 7 | |a Cardioprotection |2 Elsevier | |
| 650 | 7 | |a Labdane diterpenes |2 Elsevier | |
| 650 | 7 | |a Apoptosis |2 Elsevier | |
| 700 | 1 | |a Gómez-Gaviro, María V. |4 oth | |
| 700 | 1 | |a Benito, Yolanda |4 oth | |
| 700 | 1 | |a Barrio, Alicia |4 oth | |
| 700 | 1 | |a Bermejo, Javier |4 oth | |
| 700 | 1 | |a Fernández-Santos, María Eugenia |4 oth | |
| 700 | 1 | |a Sánchez, Pedro L. |4 oth | |
| 700 | 1 | |a Desco, Manuel |4 oth | |
| 700 | 1 | |a Fernández-Avilés, Francisco |4 oth | |
| 700 | 1 | |a Fernández-Velasco, María |4 oth | |
| 700 | 1 | |a Boscá, Lisardo |4 oth | |
| 700 | 1 | |a de las Heras, Beatriz |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier Science |a Chen, Zhuo ELSEVIER |t Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement |d 2023 |g Amsterdam [u.a.] |w (DE-627)ELV010068619 |
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10.1016/j.bcp.2014.12.011 doi GBVA2015020000027.pica (DE-627)ELV03488565X (ELSEVIER)S0006-2952(14)00725-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Cuadrado-Berrocal, Irene verfasserin aut A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Heart Elsevier Ischemia/reperfusion injury Elsevier Cardioprotection Elsevier Labdane diterpenes Elsevier Apoptosis Elsevier Gómez-Gaviro, María V. oth Benito, Yolanda oth Barrio, Alicia oth Bermejo, Javier oth Fernández-Santos, María Eugenia oth Sánchez, Pedro L. oth Desco, Manuel oth Fernández-Avilés, Francisco oth Fernández-Velasco, María oth Boscá, Lisardo oth de las Heras, Beatriz oth Enthalten in Elsevier Science Chen, Zhuo ELSEVIER Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement 2023 Amsterdam [u.a.] (DE-627)ELV010068619 volume:93 year:2015 number:4 day:15 month:02 pages:428-439 extent:12 https://doi.org/10.1016/j.bcp.2014.12.011 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_24 GBV_ILN_2002 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2018 GBV_ILN_2032 GBV_ILN_2037 GBV_ILN_2043 GBV_ILN_2091 GBV_ILN_2140 GBV_ILN_2165 GBV_ILN_2227 GBV_ILN_2285 GBV_ILN_2305 GBV_ILN_2421 GBV_ILN_2430 GBV_ILN_2520 GBV_ILN_2552 GBV_ILN_2568 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 93 2015 4 15 0215 428-439 12 045F 610 |
| spelling |
10.1016/j.bcp.2014.12.011 doi GBVA2015020000027.pica (DE-627)ELV03488565X (ELSEVIER)S0006-2952(14)00725-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Cuadrado-Berrocal, Irene verfasserin aut A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Heart Elsevier Ischemia/reperfusion injury Elsevier Cardioprotection Elsevier Labdane diterpenes Elsevier Apoptosis Elsevier Gómez-Gaviro, María V. oth Benito, Yolanda oth Barrio, Alicia oth Bermejo, Javier oth Fernández-Santos, María Eugenia oth Sánchez, Pedro L. oth Desco, Manuel oth Fernández-Avilés, Francisco oth Fernández-Velasco, María oth Boscá, Lisardo oth de las Heras, Beatriz oth Enthalten in Elsevier Science Chen, Zhuo ELSEVIER Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement 2023 Amsterdam [u.a.] (DE-627)ELV010068619 volume:93 year:2015 number:4 day:15 month:02 pages:428-439 extent:12 https://doi.org/10.1016/j.bcp.2014.12.011 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_24 GBV_ILN_2002 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2018 GBV_ILN_2032 GBV_ILN_2037 GBV_ILN_2043 GBV_ILN_2091 GBV_ILN_2140 GBV_ILN_2165 GBV_ILN_2227 GBV_ILN_2285 GBV_ILN_2305 GBV_ILN_2421 GBV_ILN_2430 GBV_ILN_2520 GBV_ILN_2552 GBV_ILN_2568 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 93 2015 4 15 0215 428-439 12 045F 610 |
| allfields_unstemmed |
10.1016/j.bcp.2014.12.011 doi GBVA2015020000027.pica (DE-627)ELV03488565X (ELSEVIER)S0006-2952(14)00725-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Cuadrado-Berrocal, Irene verfasserin aut A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Heart Elsevier Ischemia/reperfusion injury Elsevier Cardioprotection Elsevier Labdane diterpenes Elsevier Apoptosis Elsevier Gómez-Gaviro, María V. oth Benito, Yolanda oth Barrio, Alicia oth Bermejo, Javier oth Fernández-Santos, María Eugenia oth Sánchez, Pedro L. oth Desco, Manuel oth Fernández-Avilés, Francisco oth Fernández-Velasco, María oth Boscá, Lisardo oth de las Heras, Beatriz oth Enthalten in Elsevier Science Chen, Zhuo ELSEVIER Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement 2023 Amsterdam [u.a.] (DE-627)ELV010068619 volume:93 year:2015 number:4 day:15 month:02 pages:428-439 extent:12 https://doi.org/10.1016/j.bcp.2014.12.011 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_24 GBV_ILN_2002 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2018 GBV_ILN_2032 GBV_ILN_2037 GBV_ILN_2043 GBV_ILN_2091 GBV_ILN_2140 GBV_ILN_2165 GBV_ILN_2227 GBV_ILN_2285 GBV_ILN_2305 GBV_ILN_2421 GBV_ILN_2430 GBV_ILN_2520 GBV_ILN_2552 GBV_ILN_2568 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 93 2015 4 15 0215 428-439 12 045F 610 |
| allfieldsGer |
10.1016/j.bcp.2014.12.011 doi GBVA2015020000027.pica (DE-627)ELV03488565X (ELSEVIER)S0006-2952(14)00725-4 DE-627 ger DE-627 rakwb eng 610 610 DE-600 670 530 660 VZ 33.68 bkl 35.18 bkl 52.78 bkl Cuadrado-Berrocal, Irene verfasserin aut A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms 2015transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Heart Elsevier Ischemia/reperfusion injury Elsevier Cardioprotection Elsevier Labdane diterpenes Elsevier Apoptosis Elsevier Gómez-Gaviro, María V. oth Benito, Yolanda oth Barrio, Alicia oth Bermejo, Javier oth Fernández-Santos, María Eugenia oth Sánchez, Pedro L. oth Desco, Manuel oth Fernández-Avilés, Francisco oth Fernández-Velasco, María oth Boscá, Lisardo oth de las Heras, Beatriz oth Enthalten in Elsevier Science Chen, Zhuo ELSEVIER Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement 2023 Amsterdam [u.a.] (DE-627)ELV010068619 volume:93 year:2015 number:4 day:15 month:02 pages:428-439 extent:12 https://doi.org/10.1016/j.bcp.2014.12.011 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_24 GBV_ILN_2002 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2018 GBV_ILN_2032 GBV_ILN_2037 GBV_ILN_2043 GBV_ILN_2091 GBV_ILN_2140 GBV_ILN_2165 GBV_ILN_2227 GBV_ILN_2285 GBV_ILN_2305 GBV_ILN_2421 GBV_ILN_2430 GBV_ILN_2520 GBV_ILN_2552 GBV_ILN_2568 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 93 2015 4 15 0215 428-439 12 045F 610 |
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DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. Heart Elsevier Ischemia/reperfusion injury Elsevier Cardioprotection Elsevier Labdane diterpenes Elsevier Apoptosis Elsevier Gómez-Gaviro, María V. oth Benito, Yolanda oth Barrio, Alicia oth Bermejo, Javier oth Fernández-Santos, María Eugenia oth Sánchez, Pedro L. oth Desco, Manuel oth Fernández-Avilés, Francisco oth Fernández-Velasco, María oth Boscá, Lisardo oth de las Heras, Beatriz oth Enthalten in Elsevier Science Chen, Zhuo ELSEVIER Mussel-inspired adhesive friction-controlled lubricating coating for titanium alloy used in artificial joint replacement 2023 Amsterdam [u.a.] (DE-627)ELV010068619 volume:93 year:2015 number:4 day:15 month:02 pages:428-439 extent:12 https://doi.org/10.1016/j.bcp.2014.12.011 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_24 GBV_ILN_2002 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2018 GBV_ILN_2032 GBV_ILN_2037 GBV_ILN_2043 GBV_ILN_2091 GBV_ILN_2140 GBV_ILN_2165 GBV_ILN_2227 GBV_ILN_2285 GBV_ILN_2305 GBV_ILN_2421 GBV_ILN_2430 GBV_ILN_2520 GBV_ILN_2552 GBV_ILN_2568 33.68 Oberflächen Dünne Schichten Grenzflächen Physik VZ 35.18 Kolloidchemie Grenzflächenchemie VZ 52.78 Oberflächentechnik Wärmebehandlung VZ AR 93 2015 4 15 0215 428-439 12 045F 610 |
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A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms |
| abstract |
Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. |
| abstractGer |
Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. |
| abstract_unstemmed |
Abstract Therapeutic approaches to protect the heart from ischemia/reperfusion (I/R) injury are an area of intense research, as myocardial infarction is a major cause of mortality and morbidity. Diterpenes are bioactive natural products with great therapeutic potential. In the present study, we have investigated the in vivo cardioprotective effects of a labdane diterpene (DT1) against cardiac I/R injury and the molecular mechanisms involved. DT1 attenuates post-ischemic injury via an AKT-dependent activation of HIF-1α, survival pathways and inhibition of NF-κB signaling. Myocardial infarction (MI) was induced in Wistar rats occluding the left coronary artery (LCA) for 30min followed by 72h reperfusion. DT1 (5mg/kg) was intravenously administered at reperfusion. In addition, we investigated the mechanisms of cardioprotection in the Langendorff-perfused model. Cardioprotection was observed when DT1 was administered after myocardial injury. The molecular mechanisms involved the activation of the survival pathway PDK-1, AKT and AMPK, a reduced phosphorylation of PKD1/2 and sustained HIF-1α activity, leading to increased expression of anti-apoptotic proteins and decreased caspase-3 activation. Pharmacological inhibition of AKT following MI and prior to DT1 challenge significantly decreased the cardioprotection afforded by DT1 therapy at reperfusion. Cardiac function after MI was significantly improved after DT1-treatment, as evidenced by hemodynamic recovery and decreased myocardial infarct size. These findings demonstrate an efficient in vivo cardioprotection by diterpene DT1 against I/R when administered at reperfusion, opening new therapeutic strategies as adjunctive therapy for the pharmacological management of I/R injury. |
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| title_short |
A labdane diterpene exerts ex vivo and in vivo cardioprotection against post-ischemic injury: Involvement of AKT-dependent mechanisms |
| url |
https://doi.org/10.1016/j.bcp.2014.12.011 |
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Gómez-Gaviro, María V. Benito, Yolanda Barrio, Alicia Bermejo, Javier Fernández-Santos, María Eugenia Sánchez, Pedro L. Desco, Manuel Fernández-Avilés, Francisco Fernández-Velasco, María Boscá, Lisardo de las Heras, Beatriz |
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Gómez-Gaviro, María V. Benito, Yolanda Barrio, Alicia Bermejo, Javier Fernández-Santos, María Eugenia Sánchez, Pedro L. Desco, Manuel Fernández-Avilés, Francisco Fernández-Velasco, María Boscá, Lisardo de las Heras, Beatriz |
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| doi_str |
10.1016/j.bcp.2014.12.011 |
| up_date |
2024-07-06T22:14:09.414Z |
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