Role of p38 MAPK/14-3-3γ signal pathway in LPS preconditioning against cardiomyocytes anoxia/ reoxygenation injury

Aim To study the protective effect of LPS preconditioning on cardiomyocytes against anoxia/reoxygenation(A/R) injury through p38MAPK/14-3-3γ signal pathway.Methods The A/R and anoxia preconditioning APC/LPS preconditioning models of primary cultured neonatal rat myocytes were established.After treatment,the phosphor-p38MAPK and 14-3-3γ levels were detected by western blot.Meanwhile,the activity of LDH in culture medium was measured.Cell viability was detected by MTT.Apoptosis was analyzed by TUNEL.Opening of mitochondrial permeability transition pore(mPTP) was determined by Ca2+-induced swelling of isolated cardiac mitochondria.Mitochondria membrane potential was determined by flow cytometry.Results LPS preconditioning had a protective effect against following A/R injury just like APC,and phospho-p38MAPK protein and 14-3-3γ protein were elevated.Once treated by p38MAPK specific inhibitor SB203850,14-3-3γ expression was inhibited;LDH was increased and viability was decreased;apoptotic index was heightened;mPTP opening was aggravated,and mitochondria membrane potential was reduced.Conclusions LPS preconditioning has a protective effect on cardiomyocytes against A/R injury.Its mechanism may be related to activating p38MAPK and up-regulating 14-3-3γ.