Upregulation of TonEBP and COX2 expression in Hypertonicity. Effect of COX inhibitors.

FERNÁNDEZ-TOME,MARÍA, LEPERA, L. FAVALE, N, PESCIO, L, CASALI, C, AND STERIN-SPEZIALE, N..

Rosario, Santa Fe Argentina

Congreso; XLII Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular- SAIB; 2006

SAIB

Upregulation of TonEBP and COX2 expression in Hypertonicity. Effect of COX inhibitors.     Fernández-Tome,María, Lepera, L. Favale, N, Pescio, L, Casali, C, and Sterin-Speziale, N.. Biología Celular. FFyB, UBA. IQUIFIB-CONICET. Buenos Aires, ARGENTINA. email: fertome@mail.retina.ar   Renal inner medulla plays a key role in body water and electrolytic homeostasis. Such physiological actions are performed by medullary structures immersed in the highest organism interstitial osmolality. Thus, renal cells need protective mechanisms so as to preserve their integrity. TonEBP, a transcriptional activator protein, stimulates genes whose products drive cellular protection from high salt and urea concentration, osmolytes and urea transporters and Hsp70, among others. On the other hand, COX2 has been reported as a protective gene in renal tubular cells exposed to high NaCl. Thus, the aim of the present work was to evaluate the relationship between both proteins and their contribution to renal cell survival. First, we evaluated COX2 activity inhibition in MDCK cultures exposed to 150 or 250 mM NaCl. NS398 abolished COX2 prostaglandin synthesis but no effect on cell number and viability was observed. NS398 caused a concentration-dependent increase in COX2 protein which was parallel to the increase in cell number, and COX2 siRNA decreased cell survival. NS398 also increased TonEBP expression and TonEBP siRNA abolished COX2 expression and decreased cell survival. These results show that COX2 is involved in cell protection against hypertonicity by a prostaglandin independent mechanism and its expression requires TonEBP activity.