Differential effects of cholecalciferol and calcitriol on muscle proteolysis and oxidative stress in angiotensin II ‐induced C2C12 myotube atrophy

Cholecalciferol exhibited beneficial roles, whereas calcitriol possessed the negative impact on skeletal muscle proteostasis in angiotensin II-induced muscle atrophy. AbstractRenin –angiotensin system activation contributes to skeletal muscle atrophy in aging individuals with chronic diseases. We aimed to explore the effects of cholecalciferol (VD3) and calcitriol (1,25VD3) on signaling of muscle proteolysis and oxidative stress in myotubes challenged with angiotensin II (AII). The mouse C2C12 myotubes were assigned to vehicle, AII, AII  + VD3, AII  + 1,25VD3, and AII  + losartan groups. The expression levels of muscle-specific E3 ubiquitin ligase proteins, autophagy-related proteins, and oxidative stress markers were investigated. We demonstrated the diverse effects of VD3 and 1,25VD3 on AII-induced myotube atrophy. The myotube diameter was preserved by treatment with 100  nM VD3 and losartan, while 1 and 10  nM 1,25VD3 increased levels of FoxO3a, MuRF1, and atrogin-1 protein expression in myotubes exposed to AII. Treatment with AII  + 10 nM 1,25VD3 resulted in the upregulation of LC3B-II, LC3B-II/LC3B-I, and mature cathepsin L, which are autophagic marker proteins. The p62/SQSTM1 protein was downregulated and vitamin D receptor was upregulated after treatment with AII  + 10 nM 1,25VD3. A cellular redox imbalance was observed as AII  + 10 nM 1,25VD3-induced reactive oxygen species and NADPH oxidase-2 overproduction, and these changes were ...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL ARTICLE Source Type: research