title: Exogenous hydrogen sulfide restores cardioprotection of ischemic post-conditioning via inhibition of mPTP opening in the aging cardiomyocytes.
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.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China ; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, 150086 China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Emergency, Heilongjiang Provincial Hospital, Harbin, 150036 China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China.
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China ; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, 150086 China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1 Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Health Science, Lakehead University, Thunder Bay, ON P7B 5E1 Canada.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081 China ; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, 150086 China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
keywords: Aging cardiomyocytes; Hydrogen sulfide; Mitochondrial permeability transition pore; Post-conditioning