Oxidative stress and signal transduction pathways in alcoholic liver disease.
Ethanol is linked to several pathologies like alcohol liver injury, neurotoxicity, cardiomyopathy, fetal alcoholic syndrome or cancer. It is generally accepted that oxidative stress plays a central role in their pathogenesis. After chronic and excessive consumption, alcohol may accelerate oxidative mechanisms both directly via increased production of reactive oxygen species and indirectly by impairing protective mechanisms against them. Ethanol, its metabolites arising during its metabolic degradation as well as novel compounds formed via ethanol induced oxidative stress, especially during the action of the ethanol inducible microsomal cytochrome CYP2E1, may apart from direct damage to biological structures affect signal transduction pathways thus modulating and potentiating damage. Alteration of the redox status of cells following chronic ethanol misuse may have profound effects on cellular function and viability and lead to cell death and tissue damage. These changes linked to pathologic processes in the organism, are related to alteration of intracellular signaling pathways associated with protein kinases and transcription factor activation. Mainly mitogen activated protein kinase (MAPK) family, transcription factors-nuclear factor kappaB (NF-kappaB) and activating protein 1 (AP-1) are involved in the deterioration of cells and organs. The response is cell-type specific and depends on the dose of ethanol. Oxido-reduction balance, regulatory disturbances and signal transduction cascades responsible for alcoholic damage have been partially described, nevertheless, further studies are required to allow future novel diagnostic and therapeutical strategies. We are only at the beginning ...
Zima
Tomás
T
Institute of Clinical Chemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic. zimatom@mbox.cesnet.cz
Kalousová
Marta
M
D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051697:Activating Transcription Factor 1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D020928:Mitogen-Activated Protein Kinases