RRC ID 42943
著者 Nakanishi K, Dohmae N, Morishima N.
タイトル Endoplasmic reticulum stress increases myofiber formation in vitro.
ジャーナル FASEB J
Abstract Myoblast differentiation involves myoblast fusion followed by myofiber formation. We recently demonstrated that endoplasmic reticulum (ER) stress signaling occurs during myoblast differentiation in vivo. This signaling results in apoptosis in a subpopulation of myoblasts. In a cell culture model of myogenesis, inhibition of ER stress signaling blocked apoptosis and myoblast differentiation. To further examine the role of ER stress during myogenesis, we exposed cultured myoblasts to ER stress inducers during the transition from proliferation to differentiation. The stress inducers tunicamycin (an inhibitor of N-glycosylation in the ER) and thapsigargin (an inhibitor of ER-specific calcium ATPase) were used at doses that induce 40-50% apoptosis in myoblast cultures. Increased ER stress enhanced differentiation-associated apoptosis of myoblasts. It is likely that apoptosis induced by ER stress selectively eliminates vulnerable cells. We found that the surviving myoblast cells were even more resistant to apoptosis. Remarkably, the surviving cells efficiently differentiated into contracting myofibers that are rarely found in culture models of myogenesis. Our observations suggest that ER stress exerts a positive effect on myofiber formation, possibly mimicking the action of signals that drive apoptosis and differentiation in vivo. These results may provide important insight for developing therapies to improve myofiber formation.
巻・号 21(11)
ページ 2994-3003
公開日 2007-9-1
DOI 10.1096/fj.06-6408com
PII fj.06-6408com
PMID 17435177
MeSH Animals Anti-Bacterial Agents / pharmacology Apoptosis / drug effects Autocrine Communication Blotting, Western Caspases / metabolism Cell Differentiation / drug effects Cell Proliferation / drug effects Cells, Cultured Endoplasmic Reticulum / metabolism* Enzyme Inhibitors / pharmacology Mesoderm / cytology Mesoderm / drug effects Mesoderm / metabolism Muscle Fibers, Skeletal / physiology* Muscle, Skeletal / cytology Muscle, Skeletal / metabolism* Myoblasts / cytology Myoblasts / metabolism* Oxidative Stress* Thapsigargin / pharmacology Tunicamycin / pharmacology
IF 4.966
引用数 63
WOS 分野 BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 C2C12(RCB0987)