The physiological and pathological roles of hydrogen sulfide (H 2 S) in the regulation of cardiovascular functions have been recognized. H 2 S protects against the hypoxia/reoxygenation (H/R)-induced injury and apoptosis of cardiomyocytes, and ischemic post-conditioning (PC) plays an important role in cardioprotection from H/R injury in neonatal cardiomyocytes but not in aging cardiomyocytes. Whether H 2 S is involved in the recovery of PC-induced cardioprotection in aging cardiomyocytes is unclear. In the present study, we found that both H/R and PC decreased cystathionine-γ-lyase (CSE) expression and the production rate of H 2 S. Supplementation of NaHS protected against H/R-induced apoptosis, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c), and mPTP opening. The addition of NaHS also counteracted the reduction of cell viability caused by H/R and increased the phosphorylation of ERK1/2, PI3K, Akt, GSK-3β and mitochondrial membrane potential. Additionally, NaHS increased Bcl-2 expression, promoted PKC-ε translocation to the cell membrane, and activated mitochondrial ATP-sensitive K channels (mitoK ATP). PC alone did not provide cardioprotection in H/R-treated aging cardiomyocytes, which was significantly restored by the supplementation of NaHS. In conclusion, our results suggest that exogenous H 2 S restores PC-induced cardioprotection via the inhibition of mPTP opening by the activation of the ERK1/2-GSK-3β, PI3K-Akt-GSK-3β and PKC-ε-mitoK ATP pathways in aging cardiomyocytes. These findings provide a novel target for the treatment of aging ischemic cardiomyopathy.
CITATION STYLE
Li, H., Zhang, C., Sun, W., Li, L., Wu, B., Bai, S., … Xu, C. (2015). Exogenous hydrogen sulfide restores cardioprotection of ischemic post-conditioning via inhibition of mPTP opening in the aging cardiomyocytes. Cell and Bioscience, 5(1). https://doi.org/10.1186/s13578-015-0035-9
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