H2O2 Exposure Affects Myotube Stiffness and Actin Filament Polymerization.

Annals of biomedical engineering2015PMID: 25371376

View on PubMed DOI: 10.1007/s10439-014-1178-2

Animal StudyTB-500

Plain Language Summary

Characterizes how H2O2-induced oxidative stress affects the mechanical stiffness of cultured skeletal muscle myotubes and actin polymerization dynamics. Short H2O2 exposure increased myotube stiffness; prolonged exposure caused softening—reflecting biphasic actin polymerization changes. Thymosin β4, as the primary regulator of the G-actin/F-actin equilibrium, provides mechanistic context for how oxidative disruption of the TB4-managed actin pool alters cytoskeletal mechanics in ischemic muscle injury—advancing understanding of TB4's role in protecting skeletal muscle under oxidative stress.

Abstract

Skeletal muscles often experience oxidative stress in anaerobic metabolism and ischemia-reperfusion. This paper reports how oxidative stress affects the stiffness of cultured murine myotubes and their actin filaments polymerization dynamics. H2O2 was applied as an extrinsic oxidant to C2C12 myotubes. Atomic force microscopy results showed that short exposures to H2O2 apparently increased the stiffness of myotubes, but that long exposures made the cells softer. The turning point seemed to take place somewhere between 1 and 2 h of H2O2 exposure. We found that the stiffness change was probably due to actin filaments being favored for depolymerization after prolong H2O2 treatments, especially when the exposure duration exceeded 1 h and the exposure concentration reached 1.0 mM. Such depolymerization effect was associated with the down-regulation of thymosin beta 4, as well as the up-regulation of both cofilin2 and profilin1 after prolong H2O2 treatments.

Authors

Wong, Sing Wan; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T