Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation

• DOI: 10.1016/j.redox.2021.101994
• Publication Date: 2021-04-30T08:23:14Z
• Authors: Wei Ou; Yu Liang; Yu Qing; Wei Wu; Maodi Xie; Yabing Zhang; Yarong Zhang; Liwei Ji; Haiyang Yu; Tao Li
• Keywords: Cardioprotection; Homeostasis

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain be elucidated. This study was designed investigate impact of acclimation (HA) on cardiac I/R and antioxidative mechanism(s). Male adult mice were acclimated a chamber (10% oxygen [O2]) for 8 h/day 14 days, then subjected by ligation left anterior descending coronary artery 30 min reperfusion 24 h or 7 days. Our results showed that HA attenuated oxidative stress reduced infarct size hearts. cardioprotective effect coupled with elevation protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), rate-limiting enzyme pentose phosphate pathway, resulting upregulation NADPH/NADP+ GSH/GSSG couples enhancement redox homeostasis heart. Pharmacological suppression O-GlcNAcylation totally abolished influence G6PDH activity, balance post-I/R damage hearts cultured cardiomyocytes, whereby augmentation further enhanced benefits, suggesting central role HA-initiated effects. These findings, therefore, identified promising anti-I/R strategy heart proposed O-GlcNAc therapeutic target ischemic disease.