LXA₄ Increases The Expression Of Heme Oxygenase-1?HO-1? By Activation Of P38MAPK/Nrf2 Pathway In H9c2 Cardiomyocytes

Objective:To investigate HO-1 expression induced by LXA4 in H9c2 cardiomyocytes and the possible mechanisms of signal transduction pathways. Methods:H9c2 cells were exposed to hypoxia followed by reoxygenation(H/R) with or without pretreatment of LXA4,Nrf2 inhibitor ATRA,p38 MAPK inhibitor SB203580,LXA4+ATRA,LXA4+SB203580. Expressions of HO-1, Nrf2 and p38 MAPK mRNA and protein were examined by RT-PCR, Western blot and immunofluorescence staining. Expressions of P-p38 MAPK and the total p38 MAPK were examined by Western blot. Results:Compared with hypoxia/reoxygenation group, the levels of HO-1 mRNA and protein expression in H9c2 cardiomyocytes increased significantly(P<0.05).The expressions of HO-1 in H9c2 cardiomyocytes were decreased(P<0.05) after the cells were treated with ATRA or SB203580. ATRA blocked the nuclear accumulation of Nrf2 and decreased HO-1 protein expression induced by LXA4 pretreatment(P<0.05). SB203580 inhibited the phosphorylation level of p38 MAPK and decreased HO-1 protein expression induced by LXA4 pretreatment(P<0.05). Conclusion:LXA4 can induce HO-1 overexpression which has protective effect on hypoxia/reoxygenation injury of H9c2 cardiomyocytes. Its mechanism is related to the signal transduction pathway of p38MAPK/Nrf2, but not via activation of phosphatidyinositol-3-kinase or pathway of extracellular signal-regulated kinase.