Different roles of ERK(1/2) and p38 MAPK(alpha/beta) in cellular signaling during cardiomyocyte anoxia preconditioning.
- Author:
Yi-Feng HUANG
1
;
Kai-Zheng GONG
;
Zhen-Gang ZHANG
Author Information
1. Department of Cardiology, The 2nd Clinical Medical College of Yangzhou University, Yangzhou 225001.
- Publication Type:Journal Article
- MeSH:
Animals;
Animals, Newborn;
Cell Hypoxia;
Cells, Cultured;
Extracellular Signal-Regulated MAP Kinases;
physiology;
Hypoxia;
metabolism;
physiopathology;
Ischemic Preconditioning, Myocardial;
Mitogen-Activated Protein Kinase 1;
physiology;
Mitogen-Activated Protein Kinase 3;
physiology;
Myocytes, Cardiac;
cytology;
physiology;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
p38 Mitogen-Activated Protein Kinases;
physiology
- From:
Acta Physiologica Sinica
2003;55(4):454-458
- CountryChina
- Language:Chinese
-
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.
