Abstract
Objective
Cytochrome P4502E1 (CYP2E1) is expressed in human peripheral blood lymphocytes (PBLs), and previous reports have suggested the possibility of using this readily available tissue as a reporter of CYP2E1 status. To further explore the relevance of this approach we assessed CYP2E1 expression in PBLs in two contrasting conditions, chronic hepatitis C and insulin-dependent diabetes (IDD), illustrating an organ and a systemic disease, respectively.
Methods
Total RNA was isolated from extracted PBLs (hepatitis C patients + IDD) and by percutaneous needle biopsy (hepatitis C patients only). Gene expression for CYP2E1 was determined by real-time reverse-transcription polymerase chain reaction. Histological changes in liver tissue were assessed according to Ludwig's criteria.
Results
In patients with chronic hepatitis C a clear relationship was found between CYP2E1 expression in the liver and the progression of hepatic disease (both lobular inflammation and fibrosis indices), and observed variations were consistent with the preferential distribution of CYP2E1 in the lobular zone. No effect of the liver disease was, however, found at the PBL level. A statistically significant increase in mean CYP2E1 expression level was observed in the lymphocytes from poorly controlled IDD subjects compared to controls.
Conclusions
Taken together, our data indicate that the measurement of CYP2E1 expression in PBLs is not useful in liver diseases. However, in a systemic condition (IDD) this measurement can be proposed for monitoring the CYP2E1 induction in a relatively noninvasive manner. This tool should therefore be further validated in clinical field or experimental studies for CYP2E1 phenotyping purposes.
Similar content being viewed by others
References
Lieber CS (1997) Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77:517–544
Lindros KO, CaiYA, Pentilla KE (1990) Role of ethanol-inducible cytochrome P-450 IIE1 in carbon tetrachloride-induced damage to centrilobular hepatocytes from ethanol-treated rats. Hepatology 12:1092–1097
Anundi I, Lahteenmaki T, Rundgren M, Moldeus P, Lindros KO (1993) Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. Biochem Pharmacol 45:1251–1259
Wheeler CW, Wrighton SA, Guenthner TM (1992) Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA. Biochem Pharmacol 44:183–187
Amet Y, Berthou F, Fournier G, Dreano Y, Bardou L, Cledes J, Menez J-F (1997) Cytochrome P450 4A and 2E1 expression in human kidney microsomes. Biochem Pharmacol 53:765–771
Song BJ, Veech RL, Saenger P (1990) Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin-dependent diabetics. J Clin Endocrinol Metab 71:1036–1040
Raucy JL, Ingelman Sundberg M (1999) Drug metabolizing enzymes in lymphocytes. J Biochem Molecular Toxicology 13:223–226
Raucy JL, Schultz ED, Wester MR, Arora S, Johnston DE, Omdahl JL, Carpenter SP (1997) Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity. Drug Metab Dispos 25:1429–1435
Raucy JL, Schultz ED, Kearins MC, Arora S, Johnston DE, Omdahl JL, Eckmann L, Carpenter SP (1999) CYP2E1 Expression in human lymphocytes from various ethnic populations. Alcohol Clin Exp Res 23:1868–1874
Yano H, Tsutsumi M, Fukura M, Chen W-B, Shimanaka K, Tsuchishima M, Takase S, Imaoka S, Funae Y (2001) Study of cytochrome P4502E1 mRNA level of mononuclear cells in patients with alcoholic liver disease. Alcohol Clin Exp Res 25:2S–6S
Boucher P, Seree E, Vidon C, Cachefo de Souza A, Villard P-H, Chambon R, Barra Y, Vallon J-J (2000) Dietary lipids affect human ethanol-inducible CYP2E1 gene expression in vivo in mononuclear cells. Life Sci 67:1307–1316
Finnstrom N, Thorn M, Loof L, Rane A (2001) Independent patterns of cytochrome P450 gene expression in liver and blood in patients with suspected liver disease. Eur J Clin Pharmacol 57:403–409
Bellward GD, Chang T, Rodrigues B, McNeill JH, Maines S, Ryan DE, Levin W, Thomas PE (1988) Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat. Mol Pharmacol 33:140–143
Song BJ, Matsunaga T, Hardwick JP, Park SS, Veech RL, Yang CS, Gelboin HV, Gonzalez FJ (1987) Stabilization of cytochrome P450j messenger ribonucleic acid in the diabetic rat. Mol Endocrinol 1:542–547
Waziers I de, Garlatti M, Bouguet J, Beaune PH, Barouki R (1995) Insulin down-regulates cytochrome P450 2B and 2E expression at the post-transcriptional level in the rat hepatoma cell line. Mol Pharmacol 47:474–479
Woodcroft KJ, Hafner MS, Novak RF (2002) Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 35:263–273
Haufroid V, Toubeau F, Clippe A, Buysschaert M, Gala, J-L, Lison D (2001) Real-time quantification of cytochrome P4502E1 mRNA in human peripheral blood lymphocytes by reverse transcription-PCR: method and practical application. Clin Chem 47:1126–1129
Ludwig J (1993) The nomenclature of chronic active hepatitis: an obituary. Gastroenterology 105:274–278
Sumida A, Kinoshita K, Fukuda T, Matsuda H, Yamamoto I, Inaba T, Azuma J (1999) Relationship between mRNA levels quantified by reverse transcription-competitive PCR and metabolic activity of CYP3A4 and CYP2E1 in human liver. Biochem Biophys Res Commun 262:499–503
Rodriguez-Antona C, Donato MT, Preja E, Gomez-Lechon MJ, Castel JV (2001) Cytochrome P-450 mRNA expression in human liver and it relationship with enzyme activity. Arch Biochem Biophys 393:308–315
George J, Liddle C, Murray M, Byth K, Farrell GC (1995) Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis. Biochem Pharmacol 49:873–881
Powell H, Kitteringham NR, Pirmohamed M, Smith DA, Park BK (1998) Expression of cytochrome P4502E1 in human liver: assessment by mRNA, genotype and phenotype. Pharmacogenetics 8:411–421
Bastien M-C, Leblond F, Pichette V, Villeneuve J-P (2000) Differential alteration of cytochrome P450 isoenzymes in two experimental models of cirrhosis. Can J Physiol Pharmacol 78:912–919
Hannon-Fletcher MP, O'Kane MJ, Moles KW, Barnett YA, Barnett CR (2001) Lymphocyte cytochrome P450-CYP2E1 expression in human IDDM subjects. Food Chem Toxicol 39:125–132
Soh Y, Rhee H M, Sohn DH, Song BJ (1996) Immunological detection of CYP2E1 in fresh rat lymphocytes and its pretranslational induction by fasting. Biochem Biophys Res Commun 227:541–543
Acknowledgements
This study was supported by the National Fund for Scientific Research, Belgium, and by the European Commission (Environment and Health, fifth framework program, contract QLRT-1999-01368). Authors thank Dr. D. Maisin for the measurements of HbA1C. The technical assistance of F. Toubeau is also gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Haufroid, V., Ligocka, D., Buysschaert, M. et al. Cytochrome P4502E1 (CYP2E1) expression in peripheral blood lymphocytes: evaluation in hepatitis C and diabetes. Eur J Clin Pharmacol 59, 29–33 (2003). https://doi.org/10.1007/s00228-003-0566-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-003-0566-6