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dc.contributor.authorZhang, Lei
dc.contributor.authorWei, Shuang
dc.contributor.authorTang, Jun-Ming
dc.contributor.authorGuo, Ling-Yun
dc.contributor.authorZheng, Fei
dc.contributor.authorYang, Jian-Ye
dc.contributor.authorKong, Xia
dc.contributor.authorHuang, Yong-Zhang
dc.contributor.authorChen, Shi-You
dc.contributor.authorWang, Jia-Ning
dc.date.accessioned2013-06-12T14:37:07Z
dc.date.available2013-06-12T14:37:07Z
dc.date.issued2013-05-06
dc.identifier.citationJournal of Translational Medicine. 2013 May 06;11(1):113
dc.identifier.urihttp://dx.doi.org/10.1186/1479-5876-11-113
dc.identifier.urihttp://hdl.handle.net/10724/19508
dc.description.abstractAbstract Background Catalase (CAT) breaks down H2O2 into H2O and O2 to protects cells from oxidative damage. However, its translational potential is limited because exogenous CAT cannot enter living cells automatically. This study is aimed to investigate if PEP-1-CAT fusion protein can effectively protect cardiomyocytes from oxidative stress due to hypoxia/reoxygenation (H/R)-induced injury. Methods H9c2 cardomyocytes were pretreated with catalase (CAT) or PEP-1-CAT fusion protein followed by culturing in a hypoxia and re-oxygenation condition. Cell apoptosis were measured by Annexin V and PI double staining and Flow cytometry. Intracellular superoxide anion level was determined, and mitochondrial membrane potential was measured. Expression of apoptosis-related proteins including Bcl-2, Bax, Caspase-3, PARP, p38 and phospho-p38 was analyzed by western blotting. Results PEP-1-CAT protected H9c2 from H/R-induced morphological alteration and reduced the release of lactate dehydrogenase (LDH) and malondialdehyde content. Superoxide anion production was also decreased. In addition, PEP-1-CAT inhibited H9c2 apoptosis and blocked the expression of apoptosis stimulator Bax while increased the expression of Bcl-2, leading to an increased mitochondrial membrane potential. Mechanistically, PEP-1-CAT inhibited p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways, resulting in blockade of Bcl2/Bax/mitochondrial apoptotic pathway. Conclusion Our study has revealed a novel mechanism by which PEP-1-CAT protects cardiomyocyte from H/R-induced injury. PEP-1-CAT blocks Bcl2/Bax/mitochondrial apoptotic pathway by inhibiting p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways.
dc.titlePEP-1-CAT protects hypoxia/reoxygenation-induced cardiomyocyte apoptosis through multiple sigaling pathways
dc.typeJournal Article
dc.date.updated2013-06-07T12:42:49Z
dc.description.versionPeer Reviewed
dc.language.rfc3066en
dc.rights.holderLei Zhang et al.; licensee BioMed Central Ltd.


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