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Endoplasmic reticulum stress increases myofiber formation in vitro
Author(s) -
Nakanishi Keiko,
Dohmae Naoshi,
Morishima Nobuhiro
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6408com
Subject(s) - myogenesis , myocyte , endoplasmic reticulum , tunicamycin , microbiology and biotechnology , unfolded protein response , thapsigargin , apoptosis , cellular differentiation , biology , chemistry , biochemistry , gene
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 myogen‐esis, 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 ‐glycosyl‐ation 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.—Nakanishi, K., Dohmae, N., Mori‐shima, N. Endoplasmic reticulum stress increases myofiber formation in vitro. FASEB J. 21, 2994–3003 (2007)