title: CTRP3 promotes energy production by inducing mitochondrial ROS and up-expression of PGC-1α in vascular smooth muscle cells.
abstract: C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine with modulation effects on metabolism and inflammation. Adenosine triphosphate (ATP) exerts multiple biological effects in vascular smooth muscle cells (VSMCs) and energy imbalance is involved in vascular diseases. This study aimed to explore the effect of CTRP3 on energy production and its underlying mechanism in VSMCs. Our results indicated that exogenous CTRP3 increased ATP synthesis and the protein expression of oxidative phosphorylation (OXPHOS)-related molecules, including peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, sirtuin-3 (SIRT3), complex I, II, III, and V in cultured VSMCs. Depletion of endogenous CTRP3 by small interfering RNA (siRNA) reduced ATP synthesis and the expression of those molecules. PGC-1α knockdown abrogated CTRP3-induced ATP production and OXPHOS-related protein expression. Furthermore, CTRP3 increased mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential level. Pretreatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, and cyanidem-chlorophenylhydrazone, an uncoupler of OXPHOS, suppressed CTRP3-induced ROS production, PGC-1α expression and ATP synthesis. In conclusion, CTRP3 modulates mitochondrial energy production through targets of ROS and PGC-1α in VSMCs.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China.
authors: Han
authors: H
authors: Feng
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China.
authors: Jin-Yu
authors: JY
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China.
authors: Ming
authors: M
authors: Zheng
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China.
authors: Cheng-Lin
authors: CL
authors: Zhang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China.
authors: Yuan-Ming
authors: YM
authors: An
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China. Electronic address: lilyby@163.com.
authors: Li
authors: L
authors: Li
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, PR China. Electronic address: pathophy@bjmu.edu.cn.
authors: Li-Ling
authors: LL
authors: Wu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D054392:Adipokines; C000590534:C1q tumor necrosis factor-related protein 3, rat; D006360:Heat-Shock Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000111:Acetylcysteine
keywords: CTRP3; Energy metabolism; Mitochondrial reactive oxygen species; Oxidative phosphorylation; Peroxisome proliferator-activated receptor γ co-activator 1-α; Vascular smooth muscle cell