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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
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نویسنده
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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.
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منبع
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journal of the american heart association - 2016 - دوره : 5 - شماره : 9
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چکیده
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Background: hydrogen sulfide (h2s) is a gasotransmitter that regulates multiple cardiovascular functions. krüppel-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 γ-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. © 2016 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.
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کلیدواژه
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Atrial natriuretic peptide; Hydrogen sulfide; Krüppel-like factor 5; Myocardial hypertrophy; S-sulfhydration; Specificity protein 1
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آدرس
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key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing,china,department of pharmacology,school of pharmacy,nantong university,nantong, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing,china,department of pathology,jincheng people's hospital,jincheng, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing, China, key laboratory of food safety research,institute for nutritional sciences,shanghai institutes for biological sciences,chinese academy of sciences,shanghai, China, department of chemistry,washington state university,pullman,wa, United States, department of chemistry,washington state university,pullman,wa, United States, faculty of life sciences,the university of manchester, United Kingdom, cardiovascular division,department of clinical pharmacology british heart foundation centre of research excellence,faculty of life sciences and medicine,king's college london,london, United Kingdom, department of biology,laurentian university,sudbury, Canada, department of pharmacology,national university of singapore, Singapore, institute of metabolic disease,heilongjiang academy of medical science,third affiliated hospital of harbin medical university,harbin, China, department of pharmacology,centers for metabolic disease research,cardiovascular research,and thrombosis research,temple university school of medicine,philadelphia,pa, United States, department of geriatrics,first affiliated hospital of nanjing medical university,nanjing, China, key laboratory of cardiovascular disease and molecular intervention,nanjing medical university,nanjing,china,school of pharmacy,nanjing medical university,nanjing, China
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Authors
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