title: Interleukin 6 protects H(2)O(2)-induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation.
abstract: OBJECTIVE
  Hydrogen peroxide (H(2)O(2)) is a potent reactive oxygen species that causes cardiomyocytes injury. As an important cytokine, interleukin 6 (IL-6) has cardioprotective effects as it plays an essential role in the late phase of preconditioning. Our work is to investigate if IL-6 preconditioning has protective effects on neonatal rat ventricular cardiomyocytes in response to H(2)O(2) and its underlying mechanism.
  
  
  METHODS
  Gel-based comparative proteomic approach along with small interfering RNA (siRNA) and Western blot analysis was used to analyse mechanisms of IL-6 preconditioning on H(2)O(2)-induced neonatal rat ventricular cardiomyocytes injury.
  
  
  RESULTS
  IL-6 preconditioning protected cardiomyocytes against H(2)O(2)-induced cell death. Proteomic analysis showed that IL-6 pretreatment further increased the expression of prohibitin and improved the viability of cardiomyocytes exposed to H(2)O(2). Knocking down of prohibitin with siRNA abrogated this protection by increasing apoptosis rate. Tyrosine kinase inhibitor AG490 decreased signal transducers and activators of transcription 3 (STAT3) phosphorylation and down-regulated prohibitin expression in cardiomyocytes pretreated with IL-6 and exposed to H(2)O(2), which further dampened the protective effects of IL-6 preconditioning.
  
  
  CONCLUSIONS
  Our results provide direct evidence that prohibitin is a protective factor of IL-6 preconditioning in H(2)O(2)-induced neonatal rat ventricular cardiomyocytes death. The upregulation of prohibitin by IL-6 is, at least, partially regulated through STAT3 phosphorylation.
authors.affiliation: Nanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Jia
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Deng
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: Fu
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D000091402:Prohibitins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
chemical_list: D006861:Hydrogen Peroxide; D015850:Interleukin-6; D000091402:Prohibitins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; D000093242:Interleukin-6 Inhibitors; C494088:Stat3 protein, rat; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide