title: Irisin Controls Growth, Intracellular Ca2+ Signals, and Mitochondrial Thermogenesis in Cardiomyoblasts.
abstract: Exercise offers short-term and long-term health benefits, including an increased metabolic rate and energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well as increased mitochondrial biogenesis and energy expenditure. Remarkably, irisin is highly expressed in myocardium, but its physiological effects in the heart are unknown. The objective of this work is to investigate irisin's potential multifaceted effects on cardiomyoblasts and myocardium. For this purpose, H9C2 cells were treated with recombinant irisin produced in yeast cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on cell proliferation by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and on gene transcription profiles by qRT-PCR. R-irisin and hr-irisin both inhibited cell proliferation and activated genes related to cardiomyocyte metabolic function and differentiation, including myocardin, follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+ signaling and increase cellular oxygen consumption in H9C2 cells. Our study also suggests the existence of irisin-specific receptor on the membrane of H9C2 cells. In conclusion, irisin in a certain concentration rage increased myocardial cell metabolism, inhibited cell proliferation and promoted cell differentiation. These effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to activate expression of exercise-related genes such as follistatin and myocardin. This work supports the value of exercise, which promotes irisin release.
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Chao
authors: C
authors: Xie
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America; Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P. R. China.
authors: Yuan
authors: Y
authors: Zhang
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, United States of America.
authors: Tran D N
authors: TD
authors: Tran
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Hai
authors: H
authors: Wang
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Shiwu
authors: S
authors: Li
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Eva Vertes
authors: EV
authors: George
authors: Department of Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Haoyang
authors: H
authors: Zhuang
authors: Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, College of Pharmacy, University of Florida, Gainesville, FL, 32610, United States of America.
authors: Peilan
authors: P
authors: Zhang
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Avi
authors: A
authors: Kandel
authors: Department of Cell Biology and Anatomy, University of South Carolina of Medicine, Columbia, SC, 29209, United States of America.
authors: Yimu
authors: Y
authors: Lai
authors: Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan, 250012, P. R. China.
authors: Dongqi
authors: D
authors: Tang
authors: Department of Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Westley H
authors: WH
authors: Reeves
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, United States of America.
authors: Henrique
authors: H
authors: Cheng
authors: Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, College of Pharmacy, University of Florida, Gainesville, FL, 32610, United States of America.
authors: Yousong
authors: Y
authors: Ding
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, United States of America.
authors: Li-Jun
authors: LJ
authors: Yang
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D032386:Myoblasts, Cardiac / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics*
chemical_list: C571428:FNDC5 protein, mouse; D005353:Fibronectins