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HSF1对过氧化氢诱导心肌细胞坏死的保护作用及其机制研究 被引量：1

Protective Role Of Heat Shock Transcription Factor 1 On H2O2-induced Necrosis In Cardiomyocytes.
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摘要 目的探讨热休克转录因子1(heat shock transcription factor1,HSF1)能否通过负性调控高迁移率族蛋白1(high mobility group box1,HMGB1)抑制过氧化氢(H2O2)诱导的心肌细胞坏死,并探究其可能机制。方法体外培养大鼠心肌细胞,分别转染空病毒及HSF1病毒,转染48小时后采用H2O2(0.5mmol/L)干预,检测细胞坏死情况、HMGB1在细胞中的分布情况、细胞上清中HMGB1水平及c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)的磷酸化水平。结果 (1)H2O2干预6小时后,两组细胞活力显著下降(P<0.05),且HSF1组细胞活力显著高于空病毒组(P<0.05)。在相同干预条件下,H2O2使两组细胞上清中LDH水平显著升高(P<0.05),且HSF1组上清LDH水平显著低于空病毒组(P<0.05)。(2)H2O2干预6小时后,两组细胞胞浆中HMGB1荧光分布显著增加,且HSF1组胞浆中的HMGB1荧光分布显著低于空病毒组。(3)H2O2干预6小时后,两组细胞上清中HMGB1水平显著升高(P<0.05),且HSF1组上清HMGB1水平显著低于空病毒组(P<0.05)。(4)H2O2干预10分钟后,两组细胞p-JNK的表达显著升高(P<0.05),且HSF1组p-JNK的表达显著低于空病毒组(P<0.05)。结论 HSF1可能通过抑制JNK的活化阻止HMGB1移位与释放,继而减少H2O2诱导的细胞坏死。 Object To investigate whether heat shock transcription factor 1（HSF1） can reduce H2O2-induced cardiomyocyte necrosis through negatively regulating on high mobility group box 1（HMGB1） and furtherly explore the potential mechanism.Method Rat cardiac cells were cultured,respectively transfected with empty adenovirus or HSF1 adenovirus and stimulated with 0.5mmol/L H2O2.Then we determined the cell viability and the supernatant levels of LDH.And the location of HMGB1 in whole cells,the supernatant levels of HMGB1 and the c-Jun N-terminal kinase（JNK） activity were also mesured.Results（1） H2O2 significantly reduced cardiomyocyte viability in two groups（P 0.05）.And the cell viability in HSF1 group exposure to H2O2 for six hours was significantly higher than control group（P 0.05）.Simultaneously,H2O2 significantly increased the supernatant levels of LDH in two groups（P 0.05）.And after H2O2,the levels of LDH in HSF1 group were markedly decreased,as compared with control（P 0.05）.（2） HMGB1 staining by Immunofluorescence assay in two groups exposure to H2O2 for six hours was found in the cytoplasm,and HMGB1 staining in HSF1 group had lower intensity than control group.（3） Extracelluar HMGB1 levels were raised in two groups by treating with H2O2（P 0.05）.Compared with control,the levels of HMGB1 in HSF1 group were significantly decreased（P 0.05）.（4） The expression of p-JNK in two groups was significantly up-regulated at 10 minutes after H2O2（P 0.05）.And the levels of p-JNK in HSF1 group were markedly lower than control（P 0.05）.Conclusion HSF1 may suppress the translocation and the release of HMGB1 to inhibit cardiomyocyte necrosis through reducing JNK activity.
作者 虞莹 张培培 刘明 张磊 曹全 姜红 邹云增 葛均波
机构地区 复旦大学附属中山医院上海心血管疾病研究所
出处 《中国分子心脏病学杂志》 CAS 2012年第2期87-91,共5页 Molecular Cardiology of China
基金 国家自然科学基金(30871073) 上海市科委项目(09540703500)
关键词 热休克转录因子1 过氧化氢 氧化应激 高迁移率族蛋白1 Heat shock transcription factor 1 H2O2 Oxidative stress High mobility group box 1
分类号 R541 [医药卫生—心血管疾病]
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参考文献24

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共引文献2

同被引文献23

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中国分子心脏病学杂志
2012年 第2期

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