Sphingolipid signalling and liver diseases

Abstract

Sphingolipids (SLs) comprise a class of lipids with important structural functions and increasing relevance in cellular signalling. In particular, ceramide has attracted considerable attention owing to its role as a second messenger modulating several cell functions such as proliferation, gene expression, differentiation, cell cycle arrest and cell death. Increasing evidence documents the role of SLs in stress and death ligand-induced hepatocellular death, which contributes to the progression of several liver diseases including steatohepatitis, ischaemia-reperfusion liver injury or hepatocarcinogenesis. Furthermore, recent data indicate that the accumulation of SLs in specific cell subcompartments, characteristic of many sphingolipidoses, contributes to the hepatic dysfunctions that accompany these inherited diseases. Hence, the regulation of the cell biology and metabolism of SLs may open up a novel therapeutic avenue in the treatment of liver diseases. © 2007 Blackwell Munksgaard.The work presented was supported in part by the Research Center for Liver and Pancreatic Diseases, P50 AA 11999, funded by the US National Institute on Alcohol Abuse and Alcoholism; Plan Nacional de I1D grants SAF (2003-04974; 2006-06780); and FIS (04/1039) CIBER-HEPAD supported by Instituto de Salud Carlos III, Spain. M. M. is a Ramon y Cajal investigator.Peer Reviewe