title: Ethanol induced induction of cytochrome P450 2E1 and activation of mitogen activated protein kinases in peripheral blood lymphocytes.
abstract: Cytochrome P450 2E1 (CYP2E1), which induces oxidative stress that leads to alcohol-mediated toxicity in liver, is expressed in peripheral blood lymphocytes. To validate blood lymphocyte CYP2E1 as a biomarker of alcohol-induced diseases, studies were initiated to investigate similarities in CYP2E1 induction and associated cell signalling pathways in freshly prepared blood lymphocytes with the liver in rats exposed to alcohol.        Acute or chronic treatment of ethanol produced significant increase in enzyme activity and lipid peroxidation in blood lymphocytes. As observed in liver, this increase was associated with the enrichment of CYP2E1 protein and mRNA. Similar pattern of increase in the mRNA and protein expression of c-jun and c-fos was also observed in blood lymphocytes and liver. Acute exposure to ethanol activated ERK and JNK MAP kinases and c-jun in the blood lymphocytes and liver.        The present data demonstrating similarities in the induction of CYP2E1 and lipid peroxidation and activation of MAP Kinases in blood lymphocytes with liver after acute or chronic exposure of ethanol have suggested that blood lymphocytes could be used to monitor ethanol induced CYP2E1 induction and associated oxidative stress in liver.
authors: Developmental Toxicology Division, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), M.G. Marg, Lucknow, UP, India.
authors: Amit
authors: A
authors: Sharma
authors: Kumar
authors: K
authors: Saurabh
authors: Sanjay
authors: S
authors: Yadav
authors: Swatantra K
authors: SK
authors: Jain
authors: Devendra
authors: D
authors: Parmar
mesh_terms: D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D008214:Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4