Dexmedetomidine attenuates hypoxia-induced cardiomyocyte injury by promoting telomere/telomerase activity: Possible involvement of ERK1/2-Nrf2 signaling pathway.

Dexmedetomidine (Dex), an α2-adrenergic receptor (α2-AR) agonist, possesses cardioprotection against ischemic/hypoxic injury, but the exact mechanism is not fully elucidated. Since telomere/telomerase dysfunction is involved in myocardial ischemic damage, the present study aimed to investigate whether Dex ameliorates cobalt chloride (CoCl2; a hypoxia mimic agent in vitro)-induced the damage of H9c2 cardiomyocytes by improving telomere/telomerase dysfunction and further explored the underlying mechanism focusing on extracellular signal-regulated kinase (ERK1/2)-NF-E2-related factor 2 (Nrf2) signaling pathway. The result showed that Dex increased cell viability, decreased apoptosis, and reduced cardiomyocyte hypertrophy as illustrated by the decreases in cell surface area and the biomarker levels for cardiac hypertrophy including atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain ß messenger RNA (mRNA) and protein in CoCl2 -exposed H9c2 cells. Intriguingly, Dex increased the telomere length and telomerase activity as well as telomere reverse transcriptase protein and mRNA levels in H9c2 cells exposed to CoCl2 , indicating that Dex promotes telomere/telomerase function under hypoxia. In addition, Dex remarkably diminished the reactive oxygen species generation, reduced malondialdehyde content, and increased antioxidative signaling as evidenced by the increases in superoxide dismutase and plasma glutathione peroxidase activities. Furthermore, Dex increased the ratio of P-ERK1/2/T-ERK1/2 and P-Nrf2/T-Nrf2 and enhanced Nrf2 nuclear translocation in CoCl2 -subjected H9c2 cells, suggesting that Dex promotes the activation of the ERK1/2-Nrf2 signaling pathway. These novel findings indicated that Dex attenuates myocardial ischemic damage and reduces myocardial hypertrophy by promoting telomere/telomerase function, which may be associated with the activation of the ERK1/2-Nrf2 signaling pathway in vitro.