Differential Branching of the Sphingolipid Metabolic Pathways with the Stage of Development

Abstract

We have studied sphingomyelin metabolism in the papillae of neonatal (10-day-old) and adult (70-day-old) kidneys of male Wistar rats because sphingolipid second messengers generated by sphingomyelin metabolism are involved in cellular processes such as proliferation, differentiation and apoptosis. We showed that sphingomyelin and ceramide concentrations in homogenized rat papilla tissue increase with the time whereas sphingosine-1-phosphate content decreases. This is consistent with the finding of a higher biosynthesis of the latter sphingolipid in neonatal than in adult rat papillae. De novo synthetized ceramide was, however, higher in adult than in neonatal papilla homogenates probably accounting for the high ceramide content of the adult rat papilla. These results suggest an active de novo pathway not ending in sphingomyelin but instead arresting at ceramide in adult rat papilla tissue, partially metabolized into sphingosine-1-phosphate in neonatal rat papillae. The activity and the expression of sphingosine kinase, one of the enzymes involved in ceramide metabolism, was found to be higher in neonatal than adult rat kidney tissue. The intracellular distribution of sphingosine kinase was also different; in neonatal rat tissue the enzyme was predominantly associated with plasma membranes but it was cytosolic in adult rat papilla tissue. These findings seem to indicate that, in rat renal papillae, the developmental regulation of sphingosine kinase expression and activity addresses the sphingolipid metabolism to the formation of the proliferative metabolite sphingosine-1-phosphate in the neonatal period, and ceramide, which is associated with cell arrest and differentiation in the adult tissue. These data are consistent with the proliferative state necessary for tubular elongation during the neonatal period and the maintenance of the differentiated state in the adult tissue.