CONICET | Buscador de Institutos y Recursos Humanos

Sphingosine-1-phosphate, the product of Sphingosine Kinase activity, is a sphingolipid metabolite that regulates cell growth, survival and migration. It is also known to affect diuresis, natriuresis and reno-vascular contraction in rats although the mechanisms through which it affects these processes are not known. No previous report has addressed the differences among the kidney zones regarding endogenous sphingosine kinase expression and activity. Therefore we examined SK1 distribution and activity in the various kidney zones: cortex, medulla and papilla. We found that SK1 expression does not correlate with enzyme activity. Study of the expression showed that the enzyme is highly expressed in cortex, followed by medulla and papilla. However, medulla had the highest enzyme activity. In all kidney zones, SK1 expression was mainly cytosolic. Regarding enzyme activity, whereas in renal medulla, we found no difference between cytosol, membrane and nucleus, in cortex and papilla the membrane-bound enzyme presented the highest activity. SK1 distribution observed by immunohistochemical staining showed higher expression in cortical proximal convoluted epithelial cells. In medulla, the immunostaining was observed as patches of staining, whereas in papilla, the positive immunostaining was exclusively restricted to collecting duct cells. We also evaluated the effects of Bradykinin and Angiotensin II on SK1 activity.