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High glucose concentration abrogates sevoflurane post‐conditioning cardioprotection by advancing mitochondrial fission but dynamin‐related protein 1 inhibitor restores these effects
Author(s) -
Yu J.,
Maimaitili Y.,
Xie P.,
Wu J. J.,
Wang J.,
Yang Y. N.,
Ma H. P.,
Zheng H.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12812
Subject(s) - cardioprotection , mitochondrial fission , mitochondrial permeability transition pore , viability assay , pharmacology , dnm1l , mitochondrion , lactate dehydrogenase , tfam , mptp , chemistry , apoptosis , microbiology and biotechnology , biology , biochemistry , programmed cell death , ischemia , medicine , endocrinology , mitochondrial biogenesis , dopaminergic , dopamine , enzyme
Abstract Aim Hyperglycaemia‐induced cell injury is a primary cause of cardiovascular complications in patients with diabetes. In vivo studies demonstrated that sevoflurane post‐conditioning (SpostC) was cardioprotective against ischaemia/reperfusion injury, which was blocked by hyperglycaemia. This study investigated whether high glucose concentration abrogated SpostC cardioprotection in vitro by advancing mitochondrial fission and whether mitochondrial division inhibitor‐1 (Mdivi‐1) restored SpostC cardioprotection in cultured primary neonatal rat cardiomyocytes ( NCM s). Methods Primary cultured NCM s in low and high glucose concentrations were subjected to hypoxia/reoxygenation (H/R) injury. SpostC was carried out by adding 2.4% sevoflurane to the cells at the beginning of reoxygenation for 15 min. Cell viability, lactate dehydrogenase ( LDH ) level, cell death, mitochondrial morphology, mitochondrial membrane potential and mitochondrial permeability transition pore ( mPTP ) opening level, as well as fission‐ and fusion‐related proteins, were measured after H/R injury. Mdivi‐1 treatment was performed 40 min before hypoxia to inhibit DRP 1. Results SpostC protected cultured cardiomyocytes by increasing cell viability and reducing the LDH level and cell death following H/R, but high glucose concentration eliminated the cardioprotective effect. High glucose concentration abrogated SpostC cardioprotection via mitochondrial fragmentation (evidenced by decreased mitochondrial interconnectivity and elongation) and facilitation of mPTP opening. Decreased mitochondrial membrane potential was investigated with increased DRP 1, FIS 1 and MFN 2 and decreased MFN 1 and OPA 1 expressions. Mdivi‐1 (100 μ mol L −1 ) inhibited excessive mitochondrial fission and restored the cardioprotective effect of SpostC in high glucose conditions. Conclusion SpostC‐induced cardioprotection against H/R injury was impaired under high glucose concentrations, but the inhibition of excess mitochondrial fission restored these effects.