The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver.

The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver. Research Abstract Details 

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The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver. Abstract Text:

Hideyuki Kojima,Shinya Sakurai,Hitoshi Yoshiji,Masahito Uemura,Masahide Yoshikawa,Hiroshi Fukui,Hideyuki Kojima,Shinya Sakurai,Hitoshi Yoshiji,Masahito Uemura,Masahide Yoshikawa,Hiroshi Fukui,

Aim: Cholestasis has been associated with the endocytic retrieval of multidrug resistance protein 2 (Mrp2), but its mechanism is still unclear. Recent studies have indicated that radixin, a cross-linker between the actin filaments and membrane proteins, may be activated by phosphorylation and may be required for the canalicular localization of Mrp2. Methods: We investigated the role of radixin in the altered localization of Mrp2 in rat models of intrahepatic (ethinyl estradiol treatment) and extrahepatic (bile duct ligation) cholestasis using immunofluorescence microscopy. The changes in localization and expression were analyzed using Scion Image for Windows. Results: In both models, Mrp2 was localized outside as well as inside the ZO-1 staining, indicating partial dislocation from the canalicular membrane. In contrast to the steep elevation of the immunostaining intensity curves for Mrp2 in the controls, the corresponding curves in both models were broadened and flattened, confirming endocytic retrieval into the hepatocytes. Mrp2 and radixin were colocalized at the canalicular domain in the controls, whereas in both cholestatic rats they were dissociated at some canaliculi, indicating the disturbed colocalization of Mrp2 and radixin in cholestasis. The fluorescence of phosphorylated radixin, an active form of radixin, markedly decreased in both cholestatic models, which was supported by the reduced peak fluorescence intensities. Conclusion: The disturbed colocalization of Mrp2 and radixin may contribute to the endocytic retrieval of Mrp2 in cholestasis due to the failure to anchor Mrp2 in the canalicular membrane, in which the phosphorylated radixin may play a major role.

The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver. Publishing Authors By Initials

H Kojima,S Sakurai,H Yoshiji,M Uemura,M Yoshikawa,H Fukui,H Kojima,S Sakurai,H Yoshiji,M Uemura,M Yoshikawa,H Fukui,

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The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hepatology research : the official journal of the

VOLUME: 38

Page Numbers: 202-10

Journal Abbreviation: Hepatol. Res.

ISSN: 1386-6346

DAY: 6

MONTH: 08

YEAR: 2007

The role of radixin in altered localization of canalicular conjugate export pump Mrp2 in cholestatic rat liver. Information

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LANGUAGE: eng

NlmUniqueID: 9711801

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AFFILIATION: Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan.

Country: Netherlands

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MEDLINETA: Hepatol Res

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