title: [Different roles of ERK(1/2) and p38 MAPK(alpha/beta) in cellular signaling during cardiomyocyte anoxia preconditioning].
abstract: Preconditioning (PC) exhibits earlier and delayed protection. But the mechanism of cellular signaling in delayed protection of PC remains unclear. We explored the roles of ERK(1/2) and p38 MAPK(alpha/beta) (p38(alpha/beta)) in delayed protection of anoxia preconditioning (APC). The anoxia/reoxygenation (A/R) injury and APC models were established in cultured neonatal rat cardiomyocytes. An ERK(1/2) inhibitor (PD98059) and a p38(alpha/beta) blocker (SB203580) were applied and their effects on A/R and APC models were observed. The cellular contents of MDA, SOD, cell viability and LDH release was measured at the end of the study. ERK(1/2) and p38 MAPK total activity was measured by   in-gel   myelin basic protein phosphorylation assay at different points during sustained anoxia. The results obtained are as follows: (1) PD98059 (but not SB203580), administered in preconditioning anoxia phase in APC group, abolished completely the delayed protection of APC; (2) SB203580 administered in sustained anoxia phase in A/R group could relieve cell injury induced by anoxia, but not by PD98059; (3) the highest activity of ERK(1/2) and p38 MAPK induced by anoxia appeared at 4 h after the beginning of sustained anoxia. APC inhibited the over activation of both ERK(1/2) and p38 during the following sustained anoxia. These results suggest that ERK(1/2) activation during preconditioning may be an important link of cell signal transduction in the mechanism of APC delayed protection. p38(alpha/beta) activation at the preconditioning stage dose not participate in signaling of APC delayed protection. The excessive activation of p38(alpha/beta) is possibly a key factor in mediating cell injury induced by sustained anoxia. The inhibition of p38(alpha/beta) excessive activation during subsequent sustained anoxia might play a role in delayed protection mechanism of APC.
authors.affiliation: Department of Cardiology, The 2nd Clinical Medical College of Yangzhou University, Yangzhou 225001.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Huang
authors.forename: Kai-Zheng
authors.initials: KZ
authors.lastname: Gong
authors.forename: Zhen-Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases