LXA4通过p38MAPK/Nrf2信号通路诱导H9c2心肌细胞HO-1高表达
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国家自然科学基金(30973534,81173052)


LXA4 increases the expression of HO-1 by activation of p38MAPK/Nrf2 pathway in H9c2 cardiomyocytes
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    摘要:

    目的:探讨脂氧素A4(lipoxin A4,LXA4)诱导心肌细胞H9c2中血红素加氧酶(heme oxygenase,HO)-1表达可能涉及的信号转导通路-方法:分别用核因子E2相关因子2(nuclear factor-E2 related factor 2,Nrf2)的抑制剂ATRA-p38MAPK的抑制剂SB203580-LXA4联合ATRA-LXA4联合SB03580预处理H9c2细胞后进行缺氧/复氧处理,RT-PCR-Western blot-免疫荧光等检测HO-1-Nrf2以及p38MAPK mRNA和蛋白表达的变化-结果:与只行缺氧/复氧处理的细胞相比,LXA4预处理的H9c2细胞HO-1 mRNA和蛋白的表达明显升高(P < 0.05),而ATRA-SB203580分别抑制了Nrf2的聚集和p38MAPK的磷酸化(P < 0.05),从而抑制了LXA4对HO-1的诱导(P < 0.05)-结论:LXA4预处理诱导心肌细胞H9c2的HO-1高表达,具有抗缺氧/复氧损伤的作用,其机制与p38MAPK/Nrf2信号通路有关-

    Abstract:

    Objective:To investigate the possible mechanisms of signal transduction pathways of heme oxygenase(HO)-1 expression induced by lipoxin A4 (LXA4) in H9c2 cardiomyocytes. Methods:H9c2 cells were exposed to hypoxia followed by reoxygenation with or without pretreatment of LXA4,nuclear factor-E2 related factor 2 (Nrf2) inhibitor(ATRA),p38MAPK inhibitor(SB203580),LXA4 combined with ATRA,and LXA4 combined with SB203580. The mRNA transcription and protein expression of HO-1,Nrf2 and p38MAPK was examined by RT-PCR,Western blot and immunofluorescence staining. Results:Compared with hypoxia/reoxygenation group,the mRNA transcription and protein expression of HO-1 in H9c2 cardiomyocytes pretreated with LXA4 increased significantly(P < 0.05). The expression of HO-1 in H9c2 cardiomyocytes decreased (P < 0.05) after 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 p38MAPK and decreased HO-1 protein expression induced by LXA4 pretreatment(P < 0.05). Conclusion:LXA4 can induce HO-1 over-expression which has protective effect on H9c2 cardiomyocytes of hypoxia/reoxygenation injury. Its mechanism is related to p38MAPK/Nrf2 signal transduction pathways.

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周 昱,吴升华,陈筱青,唐艳荣. LXA4通过p38MAPK/Nrf2信号通路诱导H9c2心肌细胞HO-1高表达[J].南京医科大学学报(自然科学版),2012,(11):1493-1498

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  • 收稿日期:2012-08-20
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