Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1–p53 activation. (1st February 2020)

• Record Type: Journal Article
• Authors: Liu, Jing; Ai, Yongfei; Niu, Xiaolin; Shang, Fujun; Li, Zhili; Liu, Hui; Li, Wei; Ma, Wenshuai; Chen, Ruirui; Wei, Ting; Li, Xue; Li, Xiaoli
• Is Part Of: Chemico-biological interactions. Volume 317(2020)
• Publication Date: 2020-02-01
• Subjects: Heart failure -- Transverse aortic constriction -- Taurine -- SIRT1 -- p53; HF heart failure -- TAC transverse aortic constriction -- SIRT1 silent information regulator 1 -- p53 p53 tumor suppressor protein -- AC-p53 acetylated p53 -- ROS reactive oxygen species -- MDA malondialdehyde -- SOD superoxide dismutase -- Tau taurine -- WGA wheat germ agglutinin -- EX EX527 -- LVEDD left ventricular end-diastolic diameter -- LVESD left ventricular end-systolic diameter -- LVEF left ventricular ejection fraction -- LVFS fractional shortening -- Taut taurine transporter; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.108972
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Background: Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. Methods: HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD + /NADH ratio were determined by taurine and NAD + /NADH assay kit. Results: Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD + /NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. Conclusion: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1–p53 pathway. Highlights: Taurine can improve cardiac function of HF mice. Taurine concentration-dependently activated the SIRT1 expression in TAC mice. Taurine inhibited pressure overload-induced p53 acetylation via a SIRT1 pathway.