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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2008
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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. |
format | Online Article Text |
id | pubmed-3865666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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