Premium
Ceramide, Tumor Necrosis Factor and Alcohol‐Induced Liver Disease
Author(s) -
FernandezCheca José C.,
Colell Anna,
Mari Montserrat,
GarcíaRuiz Carmen
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000189285.04059.b3
Subject(s) - ceramide , mitochondrion , oxidative stress , sphingomyelin , tumor necrosis factor alpha , apoptosis , programmed cell death , microbiology and biotechnology , alcoholic liver disease , glutathione , reactive oxygen species , biology , chemistry , cancer research , biochemistry , immunology , enzyme , medicine , cholesterol , cirrhosis
A bstract : Background: The pathogenesis of alcohol‐induced liver disease (ALD) is incompletely known. One of the key processes mediating the progression of ALD involved the overproduction of tumor necrosis factor (TNF) and the susceptibility of hepatocytes to TNF‐induced apoptosis by alcohol intake. Methods: Analyze the apoptotic signaling of TNF resulting in the targeting and subsequent recruitment of mitochondria to death pathways. Results: Studies in experimental animal models of the disease have provided evidence for the role of ceramide generated from acidic sphingomyelinase in the apoptotic signaling of TNF through recruitment of mitochondria. The mitochondrial pool of glutathione (mGSH) is a vital line of defense against oxidative stress by precluding the accumulation peroxides generated endogenously within mitochondria and as a cofactor of mitochondrial antioxidant enzymes. The depletion of mGSH by alcohol has been described to determine the susceptibility of hepatocytes to TNF‐mediated cell death. Conclusions: The level of mGSH determines the fate of hepatocytes to acidic sphingomyelinase activation by TNF and hence strategies aimed to replenish mGSH or to antagonize the generation of ceramide from acidic sphingomyelinase may be of therapeutic value for ALD.