Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury

Fibroblast growth factor (FGF)-21 is a novel regulator of insulin-independent glucose transport in 3T3-L1 adipocytes and has glucose and triglyceride lowering effects in rodent models of diabetes. In this study, we found that FGF-21 can significantly attenuate ischemia-reperfusion (I/R) induced damage in H9c2 cells (rat heart). However, it is unclear which signal transduction pathway is involved in the cardioprotective effect of FGF-21. Thus, this study was designed to investigate the potential mechanism induced by FGF-21. The results showed that FGF-21 treatment prevented the oxidative stress and apoptosis associated with I/R damage by reducing the levels of superoxide anions, inhibiting glycogen synthase kinase (GSK) 3β by activating Akt phosphorylation, and recovering the levels of ATP synthase pyruvate kinase isozymes M1 and protein kinase C, thereby improving energy supply. In summary, we conclude that FGF-21 protects H9c2 cells against I/R injury mainly through the Akt-GSK-3β-caspase-3 dependent pathway, preventing oxidative stress, and recovery of the energy supply. Key words: FGF-21, myocardial ischemia-reperfusion, H9c2, proteomics, Akt, ROS, apoptosis, signaling pathway. Le facteur de croissance des fibroblastes (FGF)-21 est nouveau regulateur du transport de glucose independant de l'insuline dans les adipocytes 3T3-L1 qui diminue le glucose et les triglycerides dans des modeles de diabete chez le rongeur. Dans cette etude, nous avons trouve que le FGF-21 pouvait attenuer significativement le dommage induit par l'ischemiereperfusion (I/R) chez les cellules H9c2. Cependant, la voie de transduction impliquee dans l'effet cardioprotecteur du FGF-21 n'est pas clairement definie. Ainsi, cette etude a ete concue pour examiner le mecanisme d'action potentiel du FGF-21. Les resultats ont montre que le traitement au FGF-21 prevenait le stress oxydant et l'apoptose associes au dommage d'I/R en reduisant les anions superoxydes, inhibait la glycogene synthase kinase (GSK)-3β en activant la phosphorylation d'Akt, et restaurait l'ATP synthase, les isozymes M1 de la pyruvate kinase et la proteine kinase C afin d'ameliorer l'apport en energie. En resume, nous concluons que le FGF-21 protege les cellules H9c2 du dommage d'I/R principalement par l'intermediaire de la voie dependante d'Akt-GSK-3β-caspase-3, du stress anti-oxydant et de la restauration de l'apport energetique. [Traduit par la Redaction] Mots-cles: FGF-21, ischemie-reperfusion myocardique, H92c, proteomique, Akt, ERO, apoptose, voie de signalisation.
Introduction It has been reported that ischemia-reperfusion (I/R) injury is commonly associated with oxidative stress, and that reactive oxygen species (ROS) are the major mediators contributing to acute myocardial injury [...]