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- Title
Monocarboxylate transporter 4 protects against myocardial ischemia/reperfusion injury by inducing oxidative phosphorylation/glycolysis interconversion and inhibiting oxidative stress.
- Authors
Pan, Qiao; Xie, Xiaobo; Yuan, Qingxia
- Abstract
Myocardial ischemia/reperfusion (I/R) injury is the primary cause of heart damage in the treatment of myocardial infarction, and the imbalance of the energy metabolism in the pathogenesis of myocardial I/R is one of the main triggers of cardiac dysfunction. Monocarboxylate transporter 4 (MCT4) is a key transporter of lactate, which plays a vital role in cellular metabolism. The present study investigated the role and underlying mechanism of MCT4 in myocardial I/R injury. The results of this study showed that MCT4 was upregulated during oxygen–glucose deprivation (OGD) and restored after reoxygenation in cardiomyocytes HL‐1. Interestingly, the overexpression of MCT4 increased cell viability and decreased apoptosis of OGD/R‐induced HL‐1 cells. Furthermore, MCT4 boosted glucose uptake and lactate levels and promoted protein expression of glycolysis regulator LDHA, while also impeding oxidative phosphorylation (OXPHOS) regulators C‐MYC and NDUFB8 in OGD/R‐induced HL‐1 cells. A reduction in reactive oxygen species and oxidative stress markers malonaldehyde and superoxide dismutase was also observed within the OGD/R stimulated HL‐1 cells. Additionally, the in vivo exogenous application of MCT4 restored cardiac function, as demonstrated by the reduced infarct size and decreased myocardial apoptosis in I/R rats. OXPHOS and oxidative stress declined, while glycolysis was activated when the I/R mice were injected with AAV‐MCT4. Our findings indicate that MCT4 could exert a cardioprotective effect after myocardial I/R injury by inducing OXPHOS/glycolysis interconversion and inhibiting oxidative stress.
- Subjects
MYOCARDIAL reperfusion; REPERFUSION; MONOCARBOXYLATE transporters; MYOCARDIAL ischemia; REPERFUSION injury; OXIDATIVE stress; OXIDATIVE phosphorylation
- Publication
Clinical & Experimental Pharmacology & Physiology, 2023, Vol 50, Issue 12, p954
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.13821