RRC ID 41526
著者 Tanaka Y, Kobayashi Y, Gabazza EC, Higuchi K, Kamisako T, Kuroda M, Takeuchi K, Iwasa M, Kaito M, Adachi Y.
タイトル Increased renal expression of bilirubin glucuronide transporters in a rat model of obstructive jaundice.
ジャーナル Am J Physiol Gastrointest Liver Physiol
Abstract Regulation of bilirubin glucuronide transporters during hyperbilirubinemia in hepatic and extrahepatic tissues is not completely clear. In the present study, we evaluated the regulation of the bilirubin glucuronide transporters, multidrug resistance-associated proteins (MRP)2 and 3, in rats with obstructive jaundice. Bile duct ligation (BDL) or sham operation was performed in Wistar rats. Liver and kidneys were removed 1, 3, and 5 days after BDL (n = 4, in each group). Serum and urine were collected to measure bilirubin levels just before animal killing. MRP2 And MRP3 mRNA expressions were determined by real-time RT-PCR. Protein expression of MRP2 and MRP3 was determined by Western blotting. Renal MRP2 function was evaluated by para-aminohippurate (PAH) clearance. The effect of conjugated bilirubin, unconjugated bilirubin, human bile, and sulfate-conjugated bile acid on MRP2 gene expression was also evaluated in renal and hepatocyte cell lines. Serum bilirubin and urinary bilirubin excretion increased significantly after BDL. In the liver, the mRNA expression of MRP2 decreased 59, 86, and 82%, and its protein expression decreased 25, 74, and 93% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. In contrast, the liver expression of MRP3 mRNA increased 138, 2,137, and 3,295%, and its protein expression increased 560, 634, and 612% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. On the other hand, in the kidneys, the mRNA expression of MRP2 increased 162, 73, and 21%, and its protein expression increased 387, 558, and 472% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. PAH clearance was significantly increased after BDL. The mRNA expression of MRP2 increased in renal proximal tubular epithelial cells after treatment with conjugated bilirubin, sulfate-conjugated bile acid or human bile. Upregulation of MRP2 in the kidneys and MRP3 in the liver may be a compensatory mechanism to improve bilirubin clearance during obstructive jaundice.
巻・号 282(4)
ページ G656-62
公開日 2002-4-1
DOI 10.1152/ajpgi.00383.2001
PMID 11897625
MeSH Aged Aged, 80 and over Animals Bile Bile Ducts / surgery Bilirubin / analogs & derivatives* Bilirubin / blood Bilirubin / metabolism* Bilirubin / pharmacology Bilirubin / urine Blotting, Western Cholestasis / metabolism* Female Gene Expression* / drug effects Humans Kidney / chemistry Kidney / metabolism* Ligation Liver / chemistry Liver / metabolism Membrane Transport Proteins* Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins / analysis Multidrug Resistance-Associated Proteins / genetics* RNA, Messenger / analysis Rats Rats, Wistar p-Aminohippuric Acid / metabolism
IF 3.725
引用数 81
WOS 分野 PHYSIOLOGY GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 Hep G2