摘要
Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism.SIRT3,a mitochondria-localized sirtuin,regulates global mitochondrial lysine acetylation and preserves mitochondrial function.However,the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated.In this study,we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice.In addition,SIRT3 overexpression protected myocytes from hypertrophy,whereas SIRT3 silencing exacerbated AngⅡ-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy.Mechanistically,we identified NMNAT3(nicotinamide mononucleotide adenylyltransferase 3),the rate-limiting enzyme for mitochondrial NAD biosynthesis,as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacetylates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochondria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an important role in regulating cardiac function and a potential target for CHF.
出处
《神经药理学报》
2018年第4期80-81,共2页
Acta Neuropharmacologica
基金
This work was supported by grants from the National Natural Science Foundation of China(No.81673433,No.81026548 and No.81273499),Team item of the Natural Science Foundation of Guangdong Province(No.S2011030003190).
作者简介
Corresponding author:LIU Pei-qing,liupqing1964@yahoo.com,liupq@mail.sysu.edu.cn.Peiqing Liu,Director and Professor in Laboratory of Pharmacology&Toxicology,School of Pharmaceutical Science,Sun Yat-Sen University(SYSU).Until now,he has worked in the field of cardiovascular pharmacology and molecular biology for over 20 years,particularly in signal transduction,interaction between transcriptional factors and proteomic analysis in myocardial hypertrophy.He has published more than 200 research articles among which over 100 entered SCI,EI,ISTP,and is co-writer of 5 published monographs.As the director of New Drug R&D Center,he has established an advanced new drug evaluation and screening system and constructed a serial of new drug targets.His work was recognized by the SYSU and government,and two laboratories under his leadership,National Engineering Laboratory of Druggability Assessment and Evaluation,and Guangzhou Key Laboratory of Druggability Assessment for Biologically Active Compounds have been approved by Guangdong Province and Guangzhou City government.His research programs are supported by National Natural Science Foundation of China(NSFC),the National Science and Technology Major Project of China“Key New Drug Creation and Manufacturing Program”,Team Item of Natural Science Foundation of Guangdong Province,etc.Recently,He has also completed a new drug’s R&D for the treatment of Alzheimer’s disease in response to a program launched by the Ministry of Health of China.
