Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 466, Issue 2, Pages 300-307Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2007.07.030
Keywords
rat jejunum; oxidative stress; H2O2; O-2(-); HO; basolateral membrane; (Na+, K+)-ATPase
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Because oxidative stress is a component of gastrointestinal injury, we investigated the effect of H2O2 on transintestinal transport using isolated rat jejunum incubated in vitro. Millimolar concentrations of H2O2 inhibited all the tested parameters without inducing any cytotoxic effect. Electrophysiological experiments indicated that H2O2 decreases significantly both short circuit current and transepithelial electrical potential difference without affecting transepithelial resistance. The possibility that H2O2 could influence (Na+, K+)-ATPase activity was explored using isolated basolateral membranes. Besides H2O2 free radicals (O-2(-), HO center dot) were generated using different iron-dependent and independent systems;, (Na+, K+)-ATPase activity was inhibited after membrane exposure to all ROS tested. The inhibition was prevented by allopurinol, superoxide dismutase or desferrioxamine. Western blot analysis showed a decreased expression of the a I-subunit of (Na+, K+)-ATPase. We conclude that H2O2 may be a modulator of jejunal ion and water transport by multiple mechanisms, among which a significant inhibition of the basolateral (Na+, K+)-ATPase. (c) 2007 Elsevier Inc. All rights reserved.
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