5-Aminolevulinic acid combined with sodium ferrous citrate ameliorates H2O2-induced cardiomyocyte hypertrophy via activation of the MAPK/Nrf2/HO-1 pathway
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- 英文论文题名：5-Aminolevulinic acid combined with sodium ferrous citrate ameliorates H2O2-induced cardiomyocyte hypertrophy via activation of the MAPK/Nrf2/HO-1 pathway
- 论文作者：Zhu Ping ; Zhao Mingyi ; Guo Huiming ; Chen Jimei ; Wang Jinju ; Huang Huanlei ; Zheng Shaoyi ; Hei Mingyan ; Li Jiaxin ; Huang Shuai ; Li Jiani ; Ma Xiaotang ; Chen Yanfang ; Zhao Lingling ; Zhuang Jian
- 英文论文作者：Zhu Ping ; Zhao Mingyi ; Guo Huiming ; Chen Jimei ; Wang Jinju ; Huang Huanlei ; Zheng Shaoyi ; Hei Mingyan ; Li Jiaxin ; Huang Shuai ; Li Jiani ; Ma Xiaotang ; Chen Yanfang ; Zhao Lingling ; Zhuang Jian ; Guangdong Cardiovascular Institute ; Guangdong General Hospital ; Guangdong Academy of Medical Sciences ; Department of Pharmacology and Toxicology ; Boonshoft School of Medicine ; Wright State University ; Department of Pediatrics ; the Third Xiangya Hospital ; Central South University ; Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases ; Affiliated Hospital of Guangdong Medical College
- 年：2016
- 作者机构：Guangdong Cardiovascular Institute,Guangdong General Hospital,Guangdong Academy of Medical Sciences;Department of Pharmacology and Toxicology,Boonshoft School of Medicine,Wright State University;Department of Pediatrics,the Third Xiangya Hospital,Central South University;Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases,Affiliated Hospital of Guangdong Medical College;
- 英文论文关键词：5-aminolevulinic acid ; heme oxygenase-1 ; nuclear factor erythroid 2-related factor 2 ; cardiomyocyte
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R54
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：314k
- 原文格式：D
- 会议级别：全国
摘要
Objectives: Hydrogen peroxide(H2O2) causes cell damage via oxidative stress. Heme oxygenase-1(HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid(5-ALA) with sodium ferrous citrate(SFC) could protect cardiomyocytes from H2O2-induced hypertrophy via modulation of HO-1 expression. Methods: HL-1 cells pretreated with/without 5-ALA and SFC were exposed to H2O2 to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry, 3H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species(ROS) production was assessed by 5/6-chloromethyl-2=,7=-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2(Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. Results: 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and timedependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1/2, p38, and SAPK/JNK signaling pathways were activated and modulate 5-ALA- and SFCenhanced HO-1 expression. SB203580(p38 kinase), PD98059(ERK), or SP600125(JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H2O2-induced cardiac hypertrophy via activation of the MAPK/ Nrf2/HO-1 signaling pathway. Conclusions: In this study, we have shown that 5-ALA and SFC pretreatment protected against H2O2-induced cardiomyocyte hypertrophy through enhancing HO-1 expression, and the upregulation of HO-1 was modulated by Nrf2 and the activated MAPK signaling pathways.
Objectives: Hydrogen peroxide(H2O2) causes cell damage via oxidative stress. Heme oxygenase-1(HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid(5-ALA) with sodium ferrous citrate(SFC) could protect cardiomyocytes from H2O2-induced hypertrophy via modulation of HO-1 expression. Methods: HL-1 cells pretreated with/without 5-ALA and SFC were exposed to H2O2 to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry, 3H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species(ROS) production was assessed by 5/6-chloromethyl-2=,7=-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2(Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. Results: 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and timedependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1/2, p38, and SAPK/JNK signaling pathways were activated and modulate 5-ALA- and SFCenhanced HO-1 expression. SB203580(p38 kinase), PD98059(ERK), or SP600125(JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H2O2-induced cardiac hypertrophy via activation of the MAPK/ Nrf2/HO-1 signaling pathway. Conclusions: In this study, we have shown that 5-ALA and SFC pretreatment protected against H2O2-induced cardiomyocyte hypertrophy through enhancing HO-1 expression, and the upregulation of HO-1 was modulated by Nrf2 and the activated MAPK signaling pathways.
Objectives: Hydrogen peroxide(H2O2) causes cell damage via oxidative stress. Heme oxygenase-1(HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid(5-ALA) with sodium ferrous citrate(SFC) could protect cardiomyocytes from H2O2-induced hypertrophy via modulation of HO-1 expression. Methods: HL-1 cells pretreated with/without 5-ALA and SFC were exposed to H2O2 to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry, 3H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species(ROS) production was assessed by 5/6-chloromethyl-2=,7=-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2(Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. Results: 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and timedependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1/2, p38, and SAPK/JNK signaling pathways were activated and modulate 5-ALA- and SFCenhanced HO-1 expression. SB203580(p38 kinase), PD98059(ERK), or SP600125(JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H2O2-induced cardiac hypertrophy via activation of the MAPK/ Nrf2/HO-1 signaling pathway. Conclusions: In this study, we have shown that 5-ALA and SFC pretreatment protected against H2O2-induced cardiomyocyte hypertrophy through enhancing HO-1 expression, and the upregulation of HO-1 was modulated by Nrf2 and the activated MAPK signaling pathways.
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