TY - JOUR
T1 - Effects of thiol protease inhibitors on myoblast fusion and myofibril assembly in vitro
AU - Monoman, Carole L.
AU - Wang, Kuan
PY - 1998
Y1 - 1998
N2 - To investigate the roles of thiol proteases such as cathepsins and calpains in muscle differentiation, we have treated primary cultures of pectoralis muscle with a variety of protease inhibitors and examined the effects these agents have on myoblast fusion and myofibrillogenesis. We have found that a membrane-permeable inhibitor, E64D, has dramatic effects on both events of muscle differentiation. Cells treated with this inhibitor display gross morphological changes, severe delays in myofibril assembly, and reduced ability to fuse in culture. These morphological changes are correlated with a build up of β1-integrin throughout the cytoplasm. These effects could also be produced using NH4Cl, a lysosomotrophic agent. In addition, we show that two nonpermeable inhibitors (leupeptin and E64) slightly decrease myoblast fusion, but have no effects on the ability of the cells to form mature myofibrils. These results are discussed in terms of their relevance to the inheritable disease of muscular dystrophy and I-cell disease (mucolipodosis II).
AB - To investigate the roles of thiol proteases such as cathepsins and calpains in muscle differentiation, we have treated primary cultures of pectoralis muscle with a variety of protease inhibitors and examined the effects these agents have on myoblast fusion and myofibrillogenesis. We have found that a membrane-permeable inhibitor, E64D, has dramatic effects on both events of muscle differentiation. Cells treated with this inhibitor display gross morphological changes, severe delays in myofibril assembly, and reduced ability to fuse in culture. These morphological changes are correlated with a build up of β1-integrin throughout the cytoplasm. These effects could also be produced using NH4Cl, a lysosomotrophic agent. In addition, we show that two nonpermeable inhibitors (leupeptin and E64) slightly decrease myoblast fusion, but have no effects on the ability of the cells to form mature myofibrils. These results are discussed in terms of their relevance to the inheritable disease of muscular dystrophy and I-cell disease (mucolipodosis II).
KW - Confocal microscopy
KW - Dystrophin
KW - Integrins
KW - Myoblast fusion
KW - Myofibril assembly
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U2 - 10.1002/(SICI)1097-0169(1998)40:4<354::AID-CM4>3.0.CO;2-B
DO - 10.1002/(SICI)1097-0169(1998)40:4<354::AID-CM4>3.0.CO;2-B
M3 - Article
C2 - 9712265
AN - SCOPUS:0031928761
SN - 0886-1544
VL - 40
SP - 354
EP - 367
JO - Cell Motility and the Cytoskeleton
JF - Cell Motility and the Cytoskeleton
IS - 4
ER -