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阻塞性胆汁淤积大鼠肝细胞膜蛋白MRP3与核受体RXRα蛋白表达关系的研究 被引量:8

Relationship between hepatic membrane protein MRP3 and nuclear receptor RXRα
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摘要 目的通过体外细胞培养和建立大鼠胆管结扎(b ile duct ligation,BDL)所致阻塞性胆汁淤积动物模型,在蛋白水平观察多耐药相关蛋白MRP3(mu ltidrug resistance-assoc iated prote in 3,MRP3)和核受体RXRα(retinoid-X receptor al-pha,RXRα)表达的关系。方法用鹅去氧胆酸(chenodeoxycholic ac id,CDCA)或苯巴比妥(phenobarb ital,PB)分别刺激培养的肝癌细胞HepG2并建立DBL阻塞性胆汁淤积大鼠模型后,分别抽提HepG2细胞总蛋白、核蛋白和大鼠肝脏细胞膜蛋白和核蛋白,W estern b lot方法检测MRP3和RXRα蛋白表达水平的变化。结果在细胞水平,CDCA和PB可诱导HepG2细胞膜MRP3蛋白表达增高,并抑制细胞核RXRα蛋白表达;在动物体内,BDL大鼠肝脏MRP3明显增加,同时RXRα表达明显下降。结论肝细胞膜蛋白MRP3表达的上调可能与核受体RXRα表达抑制有关。 Objective To investigate the relationship between the hepatic membrane protein MRP3 (multidrug resistance-associated protein 3, MRP3 ) expression and the nuclear hormone receptor RXRα (retinoid-X receptor alpha, RXRα)expression in both cultured hepatoma cell HepG2 and bile duct ligated (BDL) rat liver. Methods Total cellular protein and nuclear protein were isolated from HepG2 cells induced by chenodeoxycholic acid (CDCA) or phenobarbital (PB), as well as from the liver tissue of BDL rats. The protein expressions of MRP3 and RXRα were determined by Western blotting. Results The membrane protein MRP3 expression was significantly enhanced and the nuclear receptor RXRα expression was suppressed by CDCA or PB in HepG2 cells. Similarly up-regulation of MRP3 and down-regulation of RXRα were also observed in BDL rat liver. Conclusion The up-regulation of hepatic membrane protein MRP3 may be associated with down-regulation of nuclear receptor RXRα.
出处 《第三军医大学学报》 CAS CSCD 北大核心 2006年第12期1298-1301,共4页 Journal of Third Military Medical University
基金 国家自然科学基金资助项目(30570842)~~
关键词 MRP3 RXRα BDL大鼠模型 HEPG2细胞 MRP3 RXRα BDL rat model HepG2 cell
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  • 1KULLAK-UBLICK G A,STIEGER B,MEIER P J.Enterohepatic bile salt transporters in normal physiology and liver disease[J].Gastroenterology,2004,126(1):322-342. 被引量:1
  • 2BOHAN A,CHEN W S,DENSON L A,et al.Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis[J].J Biol Chem,2003,278(38):36688-36698. 被引量:1
  • 3BOYER J L.Nuclear receptor ligands:rational and effective therapy for chronic cholestatic liver disease?[J].Gastroenterology,2005,129(2):735-740. 被引量:1
  • 4KEITEL V,BURDELSKI M,WARSKULAT U,et al.Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis[J].Hepatology,2005,41(5):1160-1172. 被引量:1
  • 5CHEN J,RAYMOND K.Nuclear receptors,bile-acid detoxification,and cholestasis[J].Lancet,2006,367(9509):454-456. 被引量:1
  • 6WAGNER M,HALILBASIC E,MARSCHALL H U,et al.CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice[J].Hepatology,2005,42(2):420-430. 被引量:1
  • 7QATANANI M,MOORE D D.CAR,the continuously advancing receptor,in drug metabolism and disease[J].Curr Drug Metab,2005,6(4):329-339. 被引量:1
  • 8ABU J,BATUWANGALA M,HERBERT K,et al.Retinoic acid and retinoid receptors:potential chemopreventive and therapeutic role in cervical cancer[J].Lancet Oncol,2005,6(9):712-720. 被引量:1

同被引文献83

  • 1陈应果,别平,祝建勇.胆红素主要转运子Mrp2在大鼠梗阻性黄疸肝脏中的表达及意义[J].第三军医大学学报,2004,26(16):1429-1431. 被引量:21
  • 2吴晓飞,孔凡民,田雨,张弓,郭仁宣.胆囊胆固醇结石患者肝细胞MRP2基因表达的半定量研究[J].中华普通外科杂志,2004,19(6):375-376. 被引量:2
  • 3马颖,姜玲玲,石如玲,刘洁.同时激活肝X受体和过氧化物酶体增殖剂激活受体α对大鼠胆汁酸合成的影响[J].中国医学科学院学报,2007,29(3):384-387. 被引量:7
  • 4Kullak Ublick GA, Beuers U. Paumgartner G. Hepatobiliary transport. J Hepatol. 2000,32:3-18. 被引量:1
  • 5Vos TA, Hooiveld GJ, Koning H, et al. Up-regulation of the multidrug resistance genes,MRPl and Mdrlb, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver. Hepatology, 1998, 28: 1637- 1644. 被引量:1
  • 6Tanaka Y, Kobayashi Y, Gabazza EC, et al. Increased renal expression of bilirubin glucuronide transporters in a rat model of obstructive jaundice. Am J Physiol Gastrointest laver Physiol,2002,282, G656- G662. 被引量:1
  • 7Keppler D, Konig J. Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis,2000,20 : 265- 272. 被引量:1
  • 8Tsujii H, Konig J, Rost D, et al. Exon intron organization of the human multidrug resistance protein 2 (MRP2) gene mutated in Dubin Johnson syndrome. Gastroenterology, 1999,117 : 653- 660. 被引量:1
  • 9Stockel B, Konig J, Nies AT, et al. Characterization of the 5'- flanking region of the human muhidrug resistance protein 2 (MRP2) gene and its regulation in comparison with the multidrug resistance protein 3(MRP3) gene. Eur J Biochem, 2000, 267,1347-1358. 被引量:1
  • 10Cherrington N J, Hartley D P, I.i N, et al. Organ distribution of multidrug resistance proteins 1,2, and 3 (MRP1,2,and 3) mRNA and hepatic induction of MRP3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther, 2002, 300:97- 104. 被引量:1

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