Regulation of xanthine dehydrogenase and xanthine oxidase activity
by hypoxia.
Poss, W. Bradley, Thomas P. Huecksteadt, Peter C. Panus, Bruce A.
Freeman, and John R. Hoidal.
Division of Pediatric Critical Care, Department of Pediatrics,
University of Utah School of Medicine and the Division of
Respiratory, Critical Care, and Occupational Pulmonary Medicine, Salt
Lake City, UT; Department of Medicine, Veterans Administration
Medical Center and the University of Utah School of Medicine, Salt
Lake City, UT; and Department of Anesthesiology, University of
Alabama, Birmingham, AL
APStracts 3:0009L, 1996.
The present study determined the effect of hypoxia on xanthine
dehydrogenase (XDH) and xanthine oxidase (XO) activity, and gene and
protein expression in cultured bovine aortic endothelial cells
(BAEC). BAEC were exposed to hypoxia (3% O2) or anoxia (0% O2) for 24
or 48 hours and to 24 hours of hypoxia followed by 24 hours of
reoxygenation. Hypoxia and anoxia exposed BAEC demonstrated a greater
than twofold increase in XDH/XO activity at 24 and 48 hours as
compared to timed controls. Hypoxic cells that were subsequently
reoxygenated in 21% O2 also demonstrated a similar increase in XDH/XO
activity versus timed controls. No differences were seen in mRNA
levels at any time point. Similarly, no difference was noted in
XDH/XO protein expression following hypoxic exposure as determined by
Western blot analysis. The increase in XDH/XO activity was not
prevented by cyclohexamide, indicating that protein synthesis was not
required. Thus, the increased XDH/XO activity observed in response to
hypoxia in the present study was due to post-translational modulation
of the enzyme.
Received 8 August 1995; accepted in final form 2 January 1996.
APS Manuscript Number L249-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96