The Regulative Role of ERK5/Bim Pathway in Hypothermal Stimulation Induced Neonatal Rat’s Cardiomyocytes Injury and Apoptosis / 中国循环杂志

ABSTRACT

Objective: To explore the regulative role of extracellular regulated protein kinase-5 (ERK5)/Bcl-2 interacting mediator of cell death (Bim) pathway in hypothermal stimulation induced neonatal rat’s cardiomyocytes (CMs) damage and apoptosis. Methods: CMs were cultured for hypothermal stimulation and the speciifc siRNA was used to down-regulate the ERK5 or Bim in CMs. The cell apoptosis was detected by lfow cytometry, protein expression was examined by Western blot analysis, the intracellular Ca2+, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated by lfuorescent labeling and lfow cytometry. Results: In hypothermal stimulated CMs, ERK5 siRNA could promote Bim protein expression, but Bim siRNA could not inlfuence ERK5, while attenuated p-ERK5 expression. ERK5 siRNA induced higher apoptosis rate, while Bim siRNA could decrease such effect. ERK5 siRNA increased the intracellular Ca2+overloading, ROS activation andΔΨm damage, while Bim siRNA played the role to against those effects in hypothermal stimulated CMs. Conclusion: Our study revealed that ERK5/Bim pathway played the important regulative roll in hypothermal stimulation induced neonatal rat’s CMs damage and apoptosis.