Ethanol and fish oil induce NFκB transactivation of the collagen α2(I) promoter through lipid peroxidation–driven activation of the PKC-PI3K-Akt pathway

作者: Natalia Nieto

DOI: 10.1002/HEP.21659

关键词:

摘要: To analyze whether fish oil, as a source of polyunsaturated fatty acids from the n-3 series, could synergize with ethanol to promote collagen I upregulation in vivo, α2(I) promoter-βGal (COL1A2-βGal) transgenic mice were fed diet enriched oil presence (ethanol group) or dextrose (control group). Ethanol-fed showed mild steatosis, increased alanine aminotransferase (ALT), aspartate (AST), nonsterified acids, and plasma alcohol levels along elevated cytochrome P450 2E1 activity, lipid peroxidation end products, low glutathione (GSH) levels, which suggested enhanced oxidant stress liver injury. Increased transactivation COL1A2 promoter assessed by βGal activity was shown vivo transfection deletion constructs for α1(I) (COL1A1) promoters vitro. Transcriptional regulation both COL1A1 validated nuclear vitro transcription run-on, northern blot analysis, quantitative polymerase chain reaction, followed subsequent protein no changes matrix metalloproteinase 13 (MMP 13). further potential mechanism upregulation, an coculture model designed primary stellate cells seeded on bottom plate Boyden chamber rest plated cell culture insert, plus added. The combination factor κB binding cocultures also resulted phosphorylation kinase C, activation PI3 kinase, Akt. addition vitamin E prevented such increase. Furthermore, inhibitors all 3 kinases blocked increase NFκB promoter; latter E. Conclusion: These results suggest that (mainly [PUFAs]) can induce I, transactivating through peroxidation-PKC-PI3K-Akt-NFκB-driven absence overt steatosis inflammation. (HEPATOLOGY 2007;45:1433–1445.)

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