41] Sphingolipid-dependent signaling in regulation of cytochrome P450 expression

Abstract

Publisher Summary This chapter describes the procedures and approaches used to investigate the role of ceramide and other sphingolipids in the suppression of CYP2C11 expression by interleukin-1 in primary rat hepatocytes. The majority of P450 gene products are down-regulated by immunomodulators, but members of the CYP4A family are induced under some circumstances. Hydrolysis of sphingomyelin (SM) to ceramide plus phosphorylcholine, catalyzed by sphingomyelinase (SMase), is an early event in cellular signaling pathways for the cytokines interleukin-1 and tumor necrosis factor-α in various cell types. A cytokine or other hormone regulates P450 expression through the SM/ceramide pathway and that hormone can elicit the hydrolysis of cellular SM, with a concomitant generation of ceramide. The cytokine-induced turnover of SM in hepatocytes is not accompanied by stoichiometric formation of ceramide under all experimental conditions.