Electrical stimulation prevents doxorubicin-induced atrophy and mitochondrial loss in cultured myotubes.

Electrical stimulation prevents doxorubicin-induced atrophy and mitochondrial loss in cultured myotubes. Am J Physiol Cell Physiol. 2019 Sep 18;: Authors: Guigni BA, Fix DK, Bivona JJ, Palmer BM, Carson JA, Toth MJ Abstract Muscle contraction may protect against the effects of chemotherapy to cause skeletal muscle atrophy, but the mechanisms underlying these benefits are unclear. To address this question, we utilized in vitro modeling of contraction and mechanotransduction in C2C12 myotubes treated with doxorubicin (DOX; 0.2 μM for 3 days). Myotubes expressed contractile proteins and organized these into functional myofilaments, as electrical field stimulation (STIM) induced intracellular calcium (Ca2+) transients and contractions, both of which were prevented by inhibition of membrane depolarization. DOX treatment reduced myotube myosin content, protein synthesis and Akt (S308) and forkhead box O3a (FoxO3a; S253) phosphorylation, and increased muscle ring fiber 1 (MuRF1) expression. STIM (1 h/d) prevented DOX-induced reductions in myotube myosin content and Akt and FoxO3a phosphorylation, as well as increases in MuRF1 expression, but did not prevent DOX-induced reductions in protein synthesis. Inhibition of myosin-actin interaction during STIM prevented contraction and the anti-atrophic effects of STIM without affecting Ca2+cycling, suggesting the beneficial effect of STIM derives from mechanotransductive pathways. Further supporti...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research