title: Oxidative stress reduces transintestinal transports and (Na+, K+) -ATPase activity in rat jejunum.
abstract: Because oxidative stress is a component of gastrointestinal injury, we investigated the effect of H(2)O(2) on transintestinal transport using isolated rat jejunum incubated in vitro. Millimolar concentrations of H(2)O(2) inhibited all the tested parameters without inducing any cytotoxic effect. Electrophysiological experiments indicated that H(2)O(2) decreases significantly both short circuit current and transepithelial electrical potential difference without affecting transepithelial resistance. The possibility that H(2)O(2) could influence (Na+, K+) -ATPase activity was explored using isolated basolateral membranes. Besides H(2)O(2), free radicals (O(2)(*-), HO*) 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 alpha(1)-subunit of (Na+, K+) -ATPase. We conclude that H(2)O(2) may be a modulator of jejunal ion and water transport by multiple mechanisms, among which a significant inhibition of the basolateral (Na+, K+) -ATPase.
authors: Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, via Celoria 26, I-20133, Milano, Italy. novella.orsenigo@unimi.it
authors: Maria Novella
authors: MN
authors: Orsenigo
authors: Alide
authors: A
authors: Faelli
authors: Cristina
authors: C
authors: Porta
authors: Chiara
authors: C
authors: Sironi
authors: Umberto
authors: U
authors: Laforenza
authors: Markus
authors: M
authors: Paulmichl
authors: Marisa
authors: M
authors: Tosco
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D000493:Allopurinol; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D003676:Deferoxamine