Khan Islam
Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait.
Nephron. 2002 May;91(1):120-8. doi: 10.1159/000057613.
Experimental colitis induces the expression of Na+-H+ exchanger (NHE) isoforms 1 and 3 in the rat colon, however, their status in rat kidney is not established.
The renal cortical NHE-1 and -3 expression was examined in the colitic rats. Since cyclooxygenase-2 (cox-2) plays an important role in inflammation, its regulatory role on these isoforms was also investigated by using a cox-2-selective phosphorothioated antisense oligonucleotide (S-oligo).
Male Sprague-Dawley rats having colitis induced by acetic acid or trinitrobenzenesulfonic acid (TNBS) were given injection of S-oligo (3 mg/kg, i.p.) and a mismatched control oligonucleotide (C-oligo) daily 2 h before inducing colitis. Colonic myeloperoxidase activity (MPO) was used to indicate colitis. The renal cortical levels of NHE-1, NHE-3 and alpha-actin, an internal control, were estimated by the Western blot analysis.
Colonic MPO activity was increased and urine output was decreased in both models of colitis. Serum, but not the renal cortical level of TNF-alpha, was increased in both cases. Only TNBS condition showed an increased PGE2 level and a decreased body weight. Water intake and renal histology remained unchanged in either case. The NHE-3 protein, localized on the proximal tubules, was increased significantly without any change in NHE-1 and alpha-actin in both cases. These changes, except the body weight, were significantly reversed by the S-oligo.
Selective induction of NHE-3 and TNF-alpha, and their reversal by cox-2 inhibition, suggest a cox-2-dependent regulation of NHE-3, which possibly involves TNF-alpha released from the site of inflammation and not from the kidney in colitis. The induction of NHE-3 is independent of the nature of colitides, and might be important to compensate for the loss of electrolyte and water in experimental colitis.
