Oxidative stress reduces transintestinal transports and (Na+, K+) -ATPase activity in rat jejunum.
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.
Orsenigo
Maria Novella
MN
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, via Celoria 26, I-20133, Milano, Italy. novella.orsenigo@unimi.it
Faelli
Alide
A
Porta
Cristina
C
Sironi
Chiara
C
Laforenza
Umberto
U
Paulmichl
Markus
M
Tosco
Marisa
M
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
D017382:Reactive Oxygen Species; D000493:Allopurinol; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D003676:Deferoxamine