Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 5; p. 1204
• Main Authors: Wanka, Heike, Lutze, Philipp, Albers, Alexander, Golchert, Janine, Staar, Doreen, Peters, Jörg
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.05.2021; MDPI
• Subjects: Angiotensin; Anoxia; Apoptosis; cardiac H9c2 cells; Cell death; cytosolic renin; Dehydrogenases; Fibrosis; Glucose; Ischemia; ischemia-induced cell death; Membrane potential; Mitochondria; mitochondrial membrane potential; Necrosis; Oxidative stress; reactive oxygen species; Renin; secretory renin; Starvation; United States > US
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10051204

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.