Chronic hypoxia, glutathione-dependent detoxication, and metabolic
instability in rat small intestine.
Legrand, Terry S., and Tak Yee Aw.
Department of Physiology and Biophysics, Louisiana State University
Medical Center, Shreveport, LA 71130
APStracts 3:0187G, 1996.
We previously showed that chronic hypoxia decreases activity of
intestinal glutathione (GSH)-dependent enzymes and is associated with
a proximal to distal gradient of enzyme activity, suggesting reduced
detoxication capacity in ileal cells. To assess whether hypoxia
affects metabolism of hydroperoxides, jejunal and ileal enterocytes
from rats exposed to air (n=11) or 10% O2 (n=9) for 10 days were
exposed to 300 [mu]M tert-butylhydroperoxide (t-BH). The initial rate
of hydroperoxide metabolism was 50-90% faster in hypoxic enterocytes,
but cell killing was enhanced. Metabolism in normoxic, but not
hypoxic cells, was enhanced 3-fold by addition of 10 mM glucose.
Hypoxic enterocytes exhibited a higher baseline GSH:GSSG ratio, but a
larger percent decrease following t-BH exposure. t-BH induced a 35
-40% decrease in protein-bound sulfhydryl groups in normoxic and
hypoxic enterocytes, but protein-SH was protected by glucose in
normoxic cells only. Metabolic response to substrate load or
hydroperoxide challenge was assessed by measurement of cellular O2
consumption. Hypoxia, but not normoxia, increases and decreases O2
consumption upon exposure to glucose and oxidant respectively,
suggesting metabolic dysregulation. In summary, prolonged O2
deficiency induces loss of intestinal metabolic integrity that is
associated with altered peroxide detoxication activity and
mitochondrial respiratory function.
Received 22 January 1996; accepted in final form 6 September
1996.
APS Manuscript Number G28-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996