Hydrogen Sulfide Regulates Krüppel-Like Factor 5 Transcription Activity via Specificity Protein 1 S-Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy
Autor: | Rui Wang, Xin Wang, Liping Xie, Xin Tang, Albert Ferro, Ming Xian, Yi Han, Zhiren Zhang, Hong Wang, Yong Ji, Yue Gu, Ying Yu, Philip K. Moore, Jieqiong Liu, Chung Min Park, Yan Ma, Guoliang Meng, Yujiao Xiao |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male lcsh:Diseases of the circulatory (Cardiovascular) system Platelet-derived growth factor myocardial hypertrophy medicine.medical_treatment Myocardial Biology hydrogen sulfide 030204 cardiovascular system & hematology Muscle hypertrophy Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Atrial natriuretic peptide Rats Inbred SHR Myocyte Myocytes Cardiac S‐sulfhydration Krüppel‐like factor 5 Original Research Platelet-Derived Growth Factor Hydrogen sulfide Angiotensin II Krüppel-like factor 5 3. Good health Hypertension Cardiology and Cardiovascular Medicine Atrial Natriuretic Factor Transcriptional Activation medicine.medical_specialty Sp1 Transcription Factor Morpholines Kruppel-Like Transcription Factors Cardiomegaly 03 medical and health sciences Internal medicine Renin–angiotensin system atrial natriuretic peptide medicine Animals Humans RNA Messenger Specificity protein 1 specificity protein 1 Sp1 transcription factor business.industry Growth factor Myocardium Cystathionine gamma-Lyase Organothiophosphorus Compounds Hypertrophy Myocardial hypertrophy S-sulfhydration equipment and supplies Rats 030104 developmental biology Endocrinology chemistry Animals Newborn Gene Expression Regulation lcsh:RC666-701 Case-Control Studies business |
Zdroj: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 5, Iss 9, Pp n/a-n/a (2016) Meng, G, Xiao, Y, Ma, Y, Tang, X, Xie, L, Liu, J, Gu, Y, Yu, Y, Park, C M, Xian, M, Wang, X, Ferro, A, Wang, R, Moore, P K, Zhang, Z, Wang, H, Han, Y & Ji, Y 2016, ' Hydrogen Sulfide Regulates Krüppel-Like Factor 5 Transcription Activity via Specificity Protein 1 S-Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy ', Journal of the American Heart Association, vol. 5, no. 9, e004160 . https://doi.org/10.1161/JAHA.116.004160 |
ISSN: | 2047-9980 |
Popis: | 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. |
Databáze: | OpenAIRE |
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