miR-21-5p Regulates Mitochondrial Respiration and Lipid Content in H9C2 Cells.

In this study we evaluated the potential for knockdown or overexpression of miR-21-5p to regulate lipid content, peroxidation and mitochondrial respiration in H9C2 cells. Cells were transfected with anti-miR-21-5p (40nM), pre-miR-21-5p (20nM) or scrambled oligonucleotide controls prior to lipid treatment in culture, or as part of the Agilent Seahorse XF fatty acid oxidation assay. Overexpression of miR-21-5p attenuated the lipid induced increase in cellular lipid content, while suppression of miR-21-5p augmented it. The abundance of malondialdehyde (MDA), a product of lipid peroxidation, was significantly increased with lipid in control cells, but attenuated in pre-miR-21-5p transfected cells. This suggests that miR-21-5p reduces oxidative stress. Cellular oxygen consumption rate (OCR) was increased in both pre-miR-21-5p and anti-miR-21-5p transfected cells. Levels of intracellular ATP were significantly higher in anti-mR-21-5p transfected cells. Pre-miR-21-5p blocked additional increases in OCR in response to etomoxir and palmitic acid. Conversely, anti-miR-21-5p transfected cells exhibited reduced OCR with both etomoxir and palmitic acid and the glycolytic capacity was concomitantly reduced. Together these results indicate that overexpression of miR-21-5p attenuates lipid content and peroxidation in H9C2 cells. This likely occurs by reducing cellular lipid uptake and utilization, shifting cellular metabolism toward reliance on the glycolytic pathway. PMID: 30657727 ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research