Upregulation of endogenous heparin-binding EGF-like growth factor and its role as a survival factor in skeletal myotubes.
To investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in skeletal muscle, we studied its function in skeletal myotubes in vitro using mouse C2C12 cells. Expression levels of membrane-anchored HB-EGF (proHB-EGF) protein were increased specifically during their differentiation among epidermal growth factor receptor (EGFR) ligands. Production levels of EGFR on the cell surface were constant. Tyrosine phosphorylation of EGFR, however, was constitutively increased during differentiation. Quenching of endogenous HB-EGF significantly rendered myotubes sensitive to apoptotic cell death induced by hypoxic stress, suggesting that proHB-EGF in the skeletal muscle is specifically upregulated to function as a survival factor.
Horikawa
M
M
Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, Japan.
Higashiyama
S
S
Nomura
S
S
Kitamura
Y
Y
Ishikawa
M
M
Taniguchi
N
N
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D015854:Up-Regulation
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors