title: Protective role of neuregulin-1 toward doxorubicin-induced myocardial toxicity.
abstract: The aim of this study was to investigate the role of the rat neuregulin-1 (NRG-1) protein in reducing doxorubicin (DOX)-induced myocardial toxicity and its underlying mechanism. The prokaryotic expression of the NRG-1 protein and the CCK8-determined activity of rat primary myocardial cells were evaluated under different DOX concentrations. Myocardial cells were divided into three groups: the control group, the 5 μM DOX (DOX5) group, and the DOX5+NRG-1 group. Western blotting was used to determine the Na+-Ca2+ exchanger (NCX-1) and cardiac myosin light-chain kinase (cMLCK) protein expression levels and real-time quantitative polymerase chain reaction methods were used to determine the mRNA expression levels. The prokaryotic expression of NRG-1 in the DOX5 group produced toxicity in the rat myocardial cells, and cell activity was significantly restored with the addition of NRG-1. The protective effect of NRG-1 was limited at higher DOX concentrations (DOX10), and the degree of cellular activity restoration was positively correlated with NRG-1 concentration. The addition of NRG-1 to DOX5 intervention inhibited NCX-1 protein and mRNA expression, and increased cMLCK protein and mRNA expression. In conclusion, DOX-induced toxicity in rat myocardial cells could be protected by NRG-1, and the mechanism may be related to the role of NRG-1 in up-regulating the cMLCK expression level and down-regulating the NCX-1 expression level.
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Duan
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: G B
authors.initials: GB
authors.lastname: Su
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China jiezhangcn@126.com.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D020890:Neuregulin-1 / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D020011:Protective Agents; D004317:Doxorubicin