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论文题目: Hydrogen Sulfide Regulates Kruppel-Like Factor 5 Transcription Activity via Specificity Protein 1 S-Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy
英文论文题目: Hydrogen Sulfide Regulates Kruppel-Like Factor 5 Transcription Activity via Specificity Protein 1 S-Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy
第一作者: Meng, GL; Xiao, YJ; Ma, Y; Tang, X; Xie, LP; Liu, JQ; Gu, Y; Yu, Y; Park, CM; Xian, M; Wang, X; Ferro, A; Wang, R; Moore, PK; Zhang, ZR; Wang, H; Han, Y; Ji, Y
英文第一作者: Meng, GL; Xiao, YJ; Ma, Y; Tang, X; Xie, LP; Liu, JQ; Gu, Y; Yu, Y; Park, CM; Xian, M; Wang, X; Ferro, A; Wang, R; Moore, PK; Zhang, ZR; Wang, H; Han, Y; Ji, Y
联系作者: Han, Y (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Geriatr, 300 Guangzhou Rd, Nanjing, Jiangsu, Peoples R China.
英文联系作者: Han, Y (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Geriatr, 300 Guangzhou Rd, Nanjing, Jiangsu, Peoples R China.
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发表年度: 2016
卷: 5
期: 9
页码: e004160
摘要: Background-Hydrogen sulfide (H2S) is a gasotransmitter that regulates multiple cardiovascular functions. Kruppel-like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H2S regulates KLF5 in myocardial hypertrophy is unknown. Methods and Results-In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H2S-releasing compound. Expression of cystathionine gamma-lyase, a principal enzyme for H2S generation in heart, decreased in human hypertrophic myocardium, whereas KLF5 expression increased. After GYY4137 administration for 4 weeks, myocardial hypertrophy was inhibited in spontaneously hypertensive rats, as demonstrated by improvement in cardiac structural parameters, heart mass, size of cardiac myocytes, and expression of atrial natriuretic peptide. H2S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H2S also inhibits platelet-derived growth factor A promoter activity, decreased recruitment of KLF5 to the platelet-derived growth factor A promoter, and reduced atrial natriuretic peptide expression in angiotensin II-stimulated cardiomyocytes, and these effects are suppressed by KLF5 knockdown. KLF5 promoter activity and KLF5 expression was also reversed by H2S. H2S increased the S-sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H2S decreased KLF5 promoter activity; reduced KLF5 mRNA expression; attenuated specificity protein 1 binding activity with KLF5 promoter; and inhibited hypertrophy after specificity protein 1 mutated at Cys659, Cys689, and Cys692 but not Cys664 overexpression. Conclusions-These findings suggest that H2S regulates KLF5 transcription activity via specificity protein 1 S-sulfhydration at Cys664 to prevent myocardial hypertrophy.
英文摘要: Background-Hydrogen sulfide (H2S) is a gasotransmitter that regulates multiple cardiovascular functions. Kruppel-like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H2S regulates KLF5 in myocardial hypertrophy is unknown. Methods and Results-In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H2S-releasing compound. Expression of cystathionine gamma-lyase, a principal enzyme for H2S generation in heart, decreased in human hypertrophic myocardium, whereas KLF5 expression increased. After GYY4137 administration for 4 weeks, myocardial hypertrophy was inhibited in spontaneously hypertensive rats, as demonstrated by improvement in cardiac structural parameters, heart mass, size of cardiac myocytes, and expression of atrial natriuretic peptide. H2S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H2S also inhibits platelet-derived growth factor A promoter activity, decreased recruitment of KLF5 to the platelet-derived growth factor A promoter, and reduced atrial natriuretic peptide expression in angiotensin II-stimulated cardiomyocytes, and these effects are suppressed by KLF5 knockdown. KLF5 promoter activity and KLF5 expression was also reversed by H2S. H2S increased the S-sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H2S decreased KLF5 promoter activity; reduced KLF5 mRNA expression; attenuated specificity protein 1 binding activity with KLF5 promoter; and inhibited hypertrophy after specificity protein 1 mutated at Cys659, Cys689, and Cys692 but not Cys664 overexpression. Conclusions-These findings suggest that H2S regulates KLF5 transcription activity via specificity protein 1 S-sulfhydration at Cys664 to prevent myocardial hypertrophy.
刊物名称: JOURNAL OF THE AMERICAN HEART ASSOCIATION
英文刊物名称: JOURNAL OF THE AMERICAN HEART ASSOCIATION
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学科: Cardiac & Cardiovascular Systems
英文学科: Cardiac & Cardiovascular Systems
影响因子: 4.863
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论文类别: Article
英文论文类别: Article
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