Abstract
The physiological and pathological roles of hydrogen sulfide (H2S) in the regulation of cardiovascular functions have been recognized. H2S 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 H2S 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 H2S. 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 (mitoKATP). 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 H2S 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-mitoKATP pathways in aging cardiomyocytes. These findings provide a novel target for the treatment of aging ischemic cardiomyopathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0035-9) contains supplementary material, which is available to authorized users.
Highlights
Myocardial ischemia/reperfusion causes cardiomyocyte injury, including cardiomyocyte apoptosis and necrosis
The primary antibodies for anti-protein kinase C (PKC)-ε, anti-cleaved caspase-3 and -9, Bcl-2, cytochrome c (Cyt c), Na+/K+ATPase, cyclin D1, p21Cip/WAF-1 and GAPDH were from Santa Cruz (Bergheimer, Germany)
Our results showed that incubation of cardiomyocytes with 10 Galactose concentration (g/L) d-galactose for 48 h significantly increased the advanced glycation end products (AGEs) content compared with other all groups
Summary
Myocardial ischemia (hypoxia)/reperfusion (reoxygenation) causes cardiomyocyte injury, including cardiomyocyte apoptosis and necrosis. Calcium overload and the adhesion of leukocytes are the main mechanisms of ischemia/reperfusion (I/R) injury. In 1986, Murry et al first reported that ischemic preconditioning (IPC) plays an important cardioprotective role against ischemia-induced injuries [1, 2]. IPC must be applied before the ischemic event, which is unpredictable, and is impractical in the clinical setting of acute myocardial infarction [3]. According to a similar regimen of brief periods of ischemia applied just after, instead of just before, sustained ischemia was shown to be as protective as preconditioning. The main theories of PC-induced protection are the preservation of mitochondrial integrity via regulation of
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