1. An alternative renin isoform is cardioprotective by modulating mitochondrial metabolism
- Author
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Philipp Lutze, Barbara Peters, Bianka Grunow, Heike Wanka, Jörg Peters, and Doreen Staar
- Subjects
0301 basic medicine ,Cardiotonic Agents ,Bioenergetics ,Cell Respiration ,Cell ,mitochondrial spare capacity ,Cell Count ,heart ,medicine.disease_cause ,Cell Line ,03 medical and health sciences ,Oxygen Consumption ,0302 clinical medicine ,Renin ,Renin–angiotensin system ,medicine ,exon(1A‐9)renin ,Animals ,Protein Isoforms ,aerobic glycolysis ,Membrane Potential, Mitochondrial ,Gene knockdown ,L-Lactate Dehydrogenase ,Chemistry ,Original Articles ,Cell Biology ,Warburg effect ,Mitochondria ,Rats ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,exon‐b renin ,H9c2 cells ,Apoptosis ,Anaerobic glycolysis ,030220 oncology & carcinogenesis ,Lactates ,Molecular Medicine ,Original Article ,cytosolic renin ,Energy Metabolism ,Glycolysis ,Oxidative stress - Abstract
The renin‐angiotensin system promotes oxidative stress, apoptosis, necrosis, fibrosis, and thus heart failure. Secretory renin plays a central role in these processes, initiating the generation of angiotensins. Nevertheless, alternative renin transcripts exist, which code for a cytosolically localized renin isoform (cyto‐renin) that is cardioprotective. We tested the hypothesis that the protective effects are associated with a beneficial switch of metabolic and mitochondrial functions. To assess H9c2 cell mitochondrial parameters, we used the Seahorse XF analyser. Cardiac H9c2 cells overexpressing cyto‐renin exhibited enhanced nonmitochondrial oxygen consumption, lactate accumulation, and LDH activity, reflecting a switch to more aerobic glycolysis known as Warburg effect. Additionally, mitochondrial spare capacity and cell respiratory control ratio were enhanced, indicating an increased potential to tolerate stress conditions. Renin knockdown induced opposite effects on mitochondrial functions without influencing metabolic parameters. Thus, the protective effects of cyto‐renin are associated with an altered bioenergetic profile and an enhanced stress tolerance, which are favourable under ischaemic conditions. Therefore, cyto‐renin is a promising new target for the prevention of ischaemia‐induced myocardial damage.
- Published
- 2018