The Role of Ceramide in the Pathogenesis of Alcoholic Liver Disease.
OBJECTIVE
Ceramide is an important second messenger in the sphingomyelin signaling pathway. In this review, we will focus on the potential role of ceramide in the pathogenesis of alcoholic liver disease (ALD).


METHODS
We have summarized the relevant studies and reviews about the role of ceramide in ALD. In addition, we have discussed the role of acid sphingomyelinase and protein phosphatase 2A in ALD, which are associated with ceramide and hepatic steatosis.


RESULTS
Recent studies have proved that the immunoreactivity and content of ceramide were increased, both in experimental models of chronic alcohol-induced steatohepatitis and human livers with severe chronic alcohol-related liver disease. Consistent with that, the levels of protein phosphatase 2A and acid sphingomyelinase were increased. Of relevance, the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was inhibited, which could block the fatty acid oxidation and promote its synthesis.


CONCLUSIONS
It was hypothesized that ethanol promoted ceramide accumulation and increased PP2A activity by activating ASMase, which may be an important mechanism in the inhibitory effect on AMPK phosphorylation and then contributed to the progression of steatosis. ASMase, a specific mechanism of ceramide generation, was proved to be a regulator of steatosis, fibrosis, lipotoxicity and endoplasmic reticulum stress.
Department of Infectious disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China.
Liu
L
Yang
Department of Infectious disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China.
Guo-Hua
GH
Jin
Department of Infectious disease, Third Hospital, Hebei Medical University, 139 ZiQiang Road, Shijiazhuang 050051, China doctorzhoujy@163.com.
Jun-Ying
JY
Zhou
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
D002518:Ceramides; D055372:AMP-Activated Protein Kinases; D054648:Protein Phosphatase 2; D013108:Sphingomyelin Phosphodiesterase