Possible Involvement Of Cyclooxygenase-2 In Hypertonic-Induced Phospholipid Synthesis

. FERNÁNDEZ TOME, MARIA DEL CARMEN; LEPERA, LEANDRO; ULLOA, JERONIMO LUIS; CASALI, CECILIA IRENE; STERIN SPEZIALE, NORMA

Pinamar,Buenos Aires, Argentina

Congreso; 10 th Congreso of Panamerican Association for Biochemistry and Molecular Biology (PABMB) and XLI Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular; 2005

Papillary cells function under physiological stress since they are submitted to the highest renal interstitial osmolality. We demonstrated that papillary tissue possesses an active phospholipid (PL) synthesis, which could act as a protective mechanism for cellular membranes in such an adverse environment. Recently, we have shown that in MDCK cultures, hypertonicity increases PL content and synthesis. Since cyclooxygenase-2 (COX2), reported as a survival protein, is involved in the maintenance of papillary PL synthesis, in the present work we explored the relationship between hypertonic-induced PL synthesis and COX-2 protein. For this purpose, confluent-arrested MDCK cultures were grown in physiological or hypertonic media (150 or 250 mM NaCl, respectively) for 24 and 48 hs, in the absence or in the presence of  NS398 (specific COX-2 inhibitor). After treatment, PL síntesis and COX-2 protein levels were evaluated. Biosynthetic activity was increased by hypertonic media. Such an increase was not blocked by NS398 and was even higher than hypertonic condition alone suggesting that COX-2 activity is not involved in biosynthetic pathway. However, westernblot experiments revealed that COX-2 protein expression was higher in hypertonic cultures treated with NS398 respect to controls. These results suggest that COX-2 specific inhibitor upregulates COX-2 protein expression which could overpass NS398 inhibitory action. Hence, hypertonic increased PL synthesis could be related to the increased COX-2 activity  contributing in this way to membrane homeostasis.