Apoptosis induced by proteasome inhibition in human myoblast cultures.
Dysfunction of the ubiquitin-proteasome system has recently been implicated in the pathogenesis of some untreatable myodegenerative diseases characterized by the formation of ubiquitinated inclusions in skeletal muscles. We have developed an in vitro model of proteasomal dysfunction by applying inhibitors of the proteasome to primary adult human skeletal muscle cultures. Our data show that proteasome inhibition causes both cytoplasmic accumulation of ubiquitinated inclusions and apoptotic death, the latter through accumulation of active caspase-3.
Sassone
J
J
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Ciammola
A
A
Tiloca
C
C
Glionna
M
M
Meola
G
G
Mancinelli
E
E
Silani
V
V
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology*; D008954:Models, Biological; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000378:metabolism
D000970:Antineoplastic Agents; D007976:Leupeptins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde