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    Signaling mechanisms in alcoholic liver injury: role of transcription factors, kinases and heat shock proteins

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    Authors
    Mandrekar, Pranoti
    UMass Chan Affiliations
    Department of Medicine, Rheumatology Division
    Liver Center
    Document Type
    Journal Article
    Publication Date
    2007-09-15
    Keywords
    Heat-Shock Proteins
    Humans
    Liver Diseases, Alcoholic
    Mitogen-Activated Protein Kinase Kinases
    Oxidative Stress
    Signal Transduction
    Toll-Like Receptors
    Transcription Factors
    Gastroenterology
    Life Sciences
    Medicine and Health Sciences
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    Abstract
    Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes, fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NFkappaB, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury.
    Source
    World J Gastroenterol. 2007 Oct 7;13(37):4979-85. Link to article on publisher's website
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38495
    PubMed ID
    17854141
    Related Resources
    Link to Article in PubMed
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    UMass Chan Faculty and Researcher Publications

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