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2003, Number 2

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Ann Hepatol 2003; 2 (2)

Alcohol-induced liver disease: when fat and oxidative stress meet

Fernández-Checa JC

Language: English
References: 61
Page: 69-75
PDF size: 71.89 Kb.


Text Extraction

Reactive oxygen species (ROS) act as signaling intermediates regulting multiple cellular processes. The fate and disposal of the signaling species are determined by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial pool of GSH (mGSH) arises from the transport of cytosol GSH by a specific mitochondrial carrier and is responsible for the maintenance of a healthy competent organelle. The depletion of mGSH upon impairment of the mitochondrial transport activity leaves mitochondria unprotected from damaging effects of ROS overgeneration within the mitochondrial electron transport chain. Tumor necrosis factor-α (TNF-α) has emerged as a key player in the progression of the alcohol-induced liver disease (ALD), and is known to target mitochondria. Key components of TNF signaling include sphingolipids, particularly ceramide generated from acidic sphingomyelinase activation serving as a source for gangliosides. In experimental models alcohol consumption enhances cholesterol levels and subsequent deposition into mitochondria resulting in selective decrease in the mGSH stores which is sufficient by itself to sensitize hepatocytes to TNF-α-mediated cell death. Thus, the combination of TNF-α overproduction, enhanced glycosphingolipid generation and selective mGSH depletion by alcohol intake cooperate making the liver sensitive to alcohol.


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