title: PEP-1-CAT protects hypoxia/reoxygenation-induced cardiomyocyte apoptosis through multiple sigaling pathways.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors: Lei
authors: L
authors: Zhang
authors: Shuang
authors: S
authors: Wei
authors: Jun-Ming
authors: JM
authors: Tang
authors: Ling-Yun
authors: LY
authors: Guo
authors: Fei
authors: F
authors: Zheng
authors: Jian-Ye
authors: JY
authors: Yang
authors: Xia
authors: X
authors: Kong
authors: Yong-Zhang
authors: YZ
authors: Huang
authors: Shi-You
authors: SY
authors: Chen
authors: Jia-Ning
authors: JN
authors: Wang
mesh_terms: D000838:Anions / Q000378:metabolism; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D000838:Anions; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013481:Superoxides; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D010100:Oxygen
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