G6PD, bond by miR-24, regulates mitochondrial dysfunction and oxidative stress in phenylephrine-induced hypertrophic cardiomyocytes.

AIMS

Pathological cardiac hypertrophy (CH) is one of the main risk factors for heart failure and cardiac death. Mitochondrial dysfunction and oxidative stress often occur in hypertrophic cardiomyocytes. It was recently proposed that deficiency or decreased activity of glucose-6-phosphate dehydrogenase (G6PD) may be related to the development of CH. This study aimed to investigate the expression of G6PD in CH and its regulatory role in mitochondrial dysfunction and oxidative stress of CH cells.

MAIN METHODS

Phenylephrine (PE) was used to create an in vitro model of CH. Using RT-qPCR and western blotting, the expression levels of target mRNAs and proteins were measured. ELISA assays and commercial kits based on spectrophotometry or colorimetry were used to measure mitochondrial function and oxidative stress. TargetScan and luciferase reporter gene assays were utilized for combination prediction and validation. CCK-8 and TUNEL kit were used to determine cell viability and apoptosis.

KEY FINDINGS

The results showed that G6PD overexpression attenuated the decreases of mitochondrial respiration, ATP, ATP synthetase and mitochondrial membrane potential induced by PE, as well as the increases of LDH release and apoptosis. Besides, PE elevated ROS activity, NO and MDA contents, and reduced SOD, CAT levels and cell viability. These effects were hindered by G6PD overexpression. MiR-24 was found to directly bind to G6PD at the motif of CUGAGCC and regulated its expression, furtherly, influenced the G6PD-mediated mitochondrial dysfunction and oxidative stress of CH cells.

SIGNIFICANCE

Generally, our study demonstrated that miR-24/G6PD regulates mitochondrial dysfunction and oxidative stress in CH cells, representing a new sight for CH therapy.