Nerol protects against hypoxia/reoxygenation-induced apoptotic injury by activating PI3K/AKT signaling in cardiomyocytes

Jin Cheng; Qing Zou; Yugang Xue

doi:10.37175/stemedicine.v2i6.87

Jin Cheng Department of Cardiology, Tangdu Hospital, Air force Military Medical University, Xi’an 710000, China
Qing Zou Department of Cardiology, Tangdu Hospital, Air force Military Medical University, Xi’an 710000, China
Yugang Xue Department of Cardiology, Tangdu Hospital, Air force Military Medical University, Xi’an 710000, China

DOI: https://doi.org/10.37175/stemedicine.v2i6.87

Keywords: Nerol, Oxidative stress, Hypoxia/reoxygenation, Apoptosis, PI3K/AKT signaling

Abstract

Background: Nerol was reported as a natural anti-oxidant product and its protective effects against cardiovascular diseases have been documented. Our current study was designed to explore the cardioprotective effect of Nerol on hypoxia/reoxygenation (H/R)-induced production of reactive oxygen species (ROS) and cell apoptosis in H9c2 cells. The potential molecular mechanisms were further investigated.

Methods: The cells were treated with 2.5 or 5 µM Nerol before or after H/R. Lactate dehydrogenase (LDH) release, cell viability, oxidative stress markers, and apoptotic proteins were assessed by cell counting kit-8, LDH release assay, commercial kits, and Western blot, respectively. To explore the underlying mechanism, the phosphorylation of p85 and p38, regulatory subunits of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK), was evaluated by Western blot. To further confirm that the PI3K/AKT signaling pathway participated in the cardiomyocyte protection, H9c2 cells were treated with 5 µM Nerol in the presence or absence of 5 µM BEZ235 or LY294002 followed by H/R treatment.

Results: H/R remarkably induced apoptosis, LDH release and ROS production. The cell viability was suppressed via inhibiting the PI3K/AKT signaling pathway activation. By contrast, pretreatment with Nerol can neutralize these effects by activating the PI3K/AKT signaling pathway. With the addition of BEZ235 or LY294002, the inhibitory effects of Nerol were abolished.

Conclusion: Nerol provided promising cardioprotective effect against H/R-induced injuries in H9c2 cells by activating the PI3K/AKT pathway.

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