Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol induces the development of hepatic steatosis, increasingly recognized as causing vulnerability to subsequent liver injury. Ethanol has been shown to activate SREBP-1 (sterol regulatory element-binding protein) processing through the conventional cholesterol-sensitive pathway (1). The present study demonstrates that ethanol can also bring about SREBP-1 cleavage and activation through a novel pathway dependent on the endoplasmic reticulum-localized caspases-4 and -12. Evidence is presented that tumor necrosis factor can stimulate caspase-4 and -12 activation in ethanol-exposed cells, which cleaves SREBP-1 to a transcriptionally active form to induce the synthesis of lipogenic enzymes and triglycerides. Moreover, the caspase-4 and -12-dependent activation of SREBP-1 is insensitive to the normal negative feedback exerted by cholesterol and is mediated by the translocation of the scaffolding protein, TRAF-2, to the endoplasmic reticulum.
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PMID:Tumor necrosis factor-alpha can provoke cleavage and activation of sterol regulatory element-binding protein in ethanol-exposed cells via a caspase-dependent pathway that is cholesterol insensitive. 1863 49