title: Follistatin-like 1 protects cardiomyoblasts from injury induced by sodium nitroprusside through modulating Akt and Smad1/5/9 signaling.
abstract: Cardiac cell apoptosis provoked by excessive sodium nitroprusside (SNP) toxicity, a potent vasodilator, limited its clinical application. Effective means for protection against SNP-induced cardiotoxicity would be highly needed. This study investigated the effects of Follistatin-like 1 (FSTL1) on the injury induced by SNP in rat cardiomyoblast H9c2 cells. First, expression of FSTL is attenuated following SNP treatment. SNP challenge significantly increases cardiac cell death, which is attenuated by FSTL1 pretreatment. Additionally, knockdown of endogenous FSTL1 enhances SNP-induced cell apoptosis. Furthermore, FSTL1 pretreatment partially inhibits SNP-induced NO generation. LY294002 and BMP4 completely abolish cytoprotective role of FSTL1 against SNP challenge, indicating both activation of Akt and inhibition of BMP/Smad1/5/9 signaling are involved in this cellular process. Lastly, FSTL1-mediated cytoprotection is independent of Smad2/3 signaling, as SB525334 fails to remove its protective role. Taken together, these results indicated that FSTL1 protects the SNP-induced injury in cardiac H9c2 cells through, at least in part, the activation of Akt and inhibition of Smad1/5/9 signaling.
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, China.
authors.forename: Weiqian
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, China.
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Orthopedic Department, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215006, China. Electronic address: uuzyshen@163.com.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D038702:Follistatin-Related Proteins / Q000378:metabolism*; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009599:Nitroprusside / Q000008:administration & dosage*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D038702:Follistatin-Related Proteins; D051896:Smad Proteins, Receptor-Regulated; D014665:Vasodilator Agents; C448719:Fstl1 protein, rat; D009599:Nitroprusside; D051058:Oncogene Protein v-akt
keywords: Akt signaling; Apoptosis; BMP/Smad1/5/9 signaling; Follistatin-like 1; Nitric oxide; Sodium nitroprusside