Regulation of atp synthase subunit e gene expression by hypoxia:
cell differentiation stage-specific control.
Levy, Fiona H., and Daniel P Kelly.
Departments of Pediatrics, Medicine, and Molecular Biology &
Pharmacology, Washington University School of Medicine, St. Louis, MO
63110
APStracts 3:0282C, 1996.
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.
Following exposure to hypoxia for 24 hours, 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 following a hypoxic exposure.
We conclude that expression of subunit e is regulated, at the pre
-translational level, by oxygen availability via cell differentiation
stage-specific mechanisms consistent with the proposed regulatory
role of this protein in cellular ATP production.
Received 18 April 1996; accepted in final form 30 August 1996.
APS Manuscript Number C212-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996