Regulation of ATP synthase subunit e gene expression by hypoxia: cell differentiation stage-specific control.
Using the technique of differential display, we identified genes that are expressed differentially under normoxic and hypoxic conditions. One regulated gene encoded subunit e of mitochondrial F1F0-ATP synthase (subunit e). The hypoxia-mediated regulation of subunit e expression in C2C12 cells was influenced by the stage of cellular differentiation. Under normoxic conditions, subunit e expression was markedly upregulated during the transition from myoblast to myotube. After exposure to hypoxia for 24 h, subunit e mRNA expression markedly decreased (>70%) in C2C12 myotubes. In contrast, subunit e mRNA levels increased slightly in response to hypoxia in C2C12 myoblasts. Studies performed with primary rat cardiocytes demonstrated that expression of subunit e mRNA and a cardiac-enriched related transcript was downregulated after a hypoxic exposure. We conclude that expression of subunit e is regulated, at the pretranslational level, by oxygen availability via cell differentiation stage-specific mechanisms consistent with the proposed regulatory role of this protein in cellular ATP production.
Levy
F H
FH
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kelly
D P
DP
D025181:ATP Synthetase Complexes; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D025181:ATP Synthetase Complexes; D017856:Phosphotransferases (Phosphate Group Acceptor)