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Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation

Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect...

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Autores principales: Song, Zhao-Feng, Ji, Xiao-Ping, Li, Xiao-Xing, Wang, Sheng-Jun, Wang, Shu-Hua, Yun-Zhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865666/
https://www.ncbi.nlm.nih.gov/pubmed/18782186
http://dx.doi.org/10.1111/j.1582-4934.2008.00183.x
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author Song, Zhao-Feng
Ji, Xiao-Ping
Li, Xiao-Xing
Wang, Sheng-Jun
Wang, Shu-Hua
Yun-Zhang,
author_facet Song, Zhao-Feng
Ji, Xiao-Ping
Li, Xiao-Xing
Wang, Sheng-Jun
Wang, Shu-Hua
Yun-Zhang,
author_sort Song, Zhao-Feng
collection PubMed
description Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect of PARP inhibition on heart I/R injury and try to elucidate the underlying mechanisms. Studies were performed with I/R rats' hearts in vivo. Ischaemia followed by reperfusion caused a significant increase in Poly (ADP-ribose) (PAR), c-Jun NH2-terminal kinase (JNK) and apoptosis-inducing factor (AIF) activity. Administration of 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), an inhibitor of PARP, decreased myocardial infarction size from 61.11±7.46%[0] to 38.83±5.67% (P<0.05) and cells apoptosis from 35±5.3% to 20±4.1% (P<0.05) and simultaneously improved the cardiac function. Western blot analysis showed that administration of DPQ reduced the activation of JNK and attenuated mitochondrial-nuclear translocation of AIF. Additionally, administration of SP600125, an inhibitor of JNK, attenuated mitochondrial-nuclear translocation of AIF. The results of the present study demonstrated that the inhibition of PARP was able to reduce heart I/R injury in vivo. Our results also suggested that JNK may be downstream of PARP activation and be required for PARP-mediated AIF translocation. Inhibition of the activity of PARP may reduce heart I/R injury via suppressing AIF translocation mediated by JNK.
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spelling pubmed-38656662015-04-27 Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation Song, Zhao-Feng Ji, Xiao-Ping Li, Xiao-Xing Wang, Sheng-Jun Wang, Shu-Hua Yun-Zhang, J Cell Mol Med Articles Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect of PARP inhibition on heart I/R injury and try to elucidate the underlying mechanisms. Studies were performed with I/R rats' hearts in vivo. Ischaemia followed by reperfusion caused a significant increase in Poly (ADP-ribose) (PAR), c-Jun NH2-terminal kinase (JNK) and apoptosis-inducing factor (AIF) activity. Administration of 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), an inhibitor of PARP, decreased myocardial infarction size from 61.11±7.46%[0] to 38.83±5.67% (P<0.05) and cells apoptosis from 35±5.3% to 20±4.1% (P<0.05) and simultaneously improved the cardiac function. Western blot analysis showed that administration of DPQ reduced the activation of JNK and attenuated mitochondrial-nuclear translocation of AIF. Additionally, administration of SP600125, an inhibitor of JNK, attenuated mitochondrial-nuclear translocation of AIF. The results of the present study demonstrated that the inhibition of PARP was able to reduce heart I/R injury in vivo. Our results also suggested that JNK may be downstream of PARP activation and be required for PARP-mediated AIF translocation. Inhibition of the activity of PARP may reduce heart I/R injury via suppressing AIF translocation mediated by JNK. Blackwell Publishing Ltd 2008-08 2008-08-11 /pmc/articles/PMC3865666/ /pubmed/18782186 http://dx.doi.org/10.1111/j.1582-4934.2008.00183.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Articles
Song, Zhao-Feng
Ji, Xiao-Ping
Li, Xiao-Xing
Wang, Sheng-Jun
Wang, Shu-Hua
Yun-Zhang,
Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title_full Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title_fullStr Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title_full_unstemmed Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title_short Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation
title_sort inhibition of the activity of poly (adp-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing jnk-mediated aif translocation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865666/
https://www.ncbi.nlm.nih.gov/pubmed/18782186
http://dx.doi.org/10.1111/j.1582-4934.2008.00183.x
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