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
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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