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Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy
BACKGROUND: Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel‐like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H(2)S regulates KLF5 in myocardial hypertrophy is unknown. METHODS AND RESULTS: In our study...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079055/ https://www.ncbi.nlm.nih.gov/pubmed/27638782 http://dx.doi.org/10.1161/JAHA.116.004160 |
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author | Meng, Guoliang Xiao, Yujiao Ma, Yan Tang, Xin Xie, Liping Liu, Jieqiong Gu, Yue Yu, Ying Park, Chung‐Min Xian, Ming Wang, Xin Ferro, Albert Wang, Rui Moore, Philip K. Zhang, Zhiren Wang, Hong Han, Yi Ji, Yong |
author_facet | Meng, Guoliang Xiao, Yujiao Ma, Yan Tang, Xin Xie, Liping Liu, Jieqiong Gu, Yue Yu, Ying Park, Chung‐Min Xian, Ming Wang, Xin Ferro, Albert Wang, Rui Moore, Philip K. Zhang, Zhiren Wang, Hong Han, Yi Ji, Yong |
author_sort | Meng, Guoliang |
collection | PubMed |
description | BACKGROUND: Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel‐like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H(2)S 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 H(2)S‐releasing compound. Expression of cystathionine γ‐lyase, a principal enzyme for H(2)S 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. H(2)S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H(2)S 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 H(2)S. H(2)S increased the S‐sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H(2)S 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 H(2)S regulates KLF5 transcription activity via specificity protein 1 S‐sulfhydration at Cys664 to prevent myocardial hypertrophy. |
format | Online Article Text |
id | pubmed-5079055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50790552016-10-28 Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy Meng, Guoliang Xiao, Yujiao Ma, Yan Tang, Xin Xie, Liping Liu, Jieqiong Gu, Yue Yu, Ying Park, Chung‐Min Xian, Ming Wang, Xin Ferro, Albert Wang, Rui Moore, Philip K. Zhang, Zhiren Wang, Hong Han, Yi Ji, Yong J Am Heart Assoc Original Research BACKGROUND: Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel‐like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H(2)S 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 H(2)S‐releasing compound. Expression of cystathionine γ‐lyase, a principal enzyme for H(2)S 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. H(2)S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H(2)S 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 H(2)S. H(2)S increased the S‐sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H(2)S 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 H(2)S regulates KLF5 transcription activity via specificity protein 1 S‐sulfhydration at Cys664 to prevent myocardial hypertrophy. John Wiley and Sons Inc. 2016-09-16 /pmc/articles/PMC5079055/ /pubmed/27638782 http://dx.doi.org/10.1161/JAHA.116.004160 Text en © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Research Meng, Guoliang Xiao, Yujiao Ma, Yan Tang, Xin Xie, Liping Liu, Jieqiong Gu, Yue Yu, Ying Park, Chung‐Min Xian, Ming Wang, Xin Ferro, Albert Wang, Rui Moore, Philip K. Zhang, Zhiren Wang, Hong Han, Yi Ji, Yong Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title | Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title_full | Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title_fullStr | Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title_full_unstemmed | Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title_short | Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy |
title_sort | hydrogen sulfide regulates krüppel‐like factor 5 transcription activity via specificity protein 1 s‐sulfhydration at cys664 to prevent myocardial hypertrophy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079055/ https://www.ncbi.nlm.nih.gov/pubmed/27638782 http://dx.doi.org/10.1161/JAHA.116.004160 |
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