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) |