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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/G682    most recent ajpgi.90226.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Calamita, G. Articles by Svelto, M. PubMed PubMed Citation Articles by Calamita, G. Articles by Svelto, M.

LIVER AND BILIARY TRACT

Altered expression and distribution of aquaporin-9 in the liver of rat with obstructive extrahepatic cholestasis

¹Dipartimento di Fisiologia Generale ed Ambientale, ²Dipartimento di Zoologia, and ⁴Dipartimento di Medicina Interna e Medicina Pubblica, Università degli Studi di Bari, Bari, Italy; and ³Instituto de Fisiología Experimental, Universidad Nacional de Rosario, Rosario, Argentina

Submitted 7 March 2008 ; accepted in final form 28 July 2008

Rat hepatocytes express aquaporin-9 (AQP9), a basolateral channel permeable to water, glycerol, and other small neutral solutes. Although liver AQP9 is known for mediating the uptake of sinusoidal blood glycerol, its relevance in bile secretion physiology and pathophysiology remains elusive. Here, we evaluated whether defective expression of AQP9 is associated to secretory dysfunction of rat hepatocytes following bile duct ligation (BDL). By immunoblotting, 1-day BDL resulted in a slight decrease of AQP9 protein in basolateral membranes and a simultaneous increase of AQP9 in intracellular membranes. This pattern was steadily accentuated in the subsequent days of BDL since at 7 days BDL basolateral membrane AQP9 decreased by 85% whereas intracellular AQP9 increased by 115%. However, the AQP9 immunoreactivity of the total liver membranes from day 7 of BDL rats was reduced by 49% compared with the sham counterpart. Results were confirmed by immunofluorescence and immunogold electron microscopy and consistent with biophysical studies showing considerable decrease of the basolateral membrane water and glycerol permeabilities of cholestatic hepatocytes. The AQP9 mRNA was slightly reduced only at day 7 of BDL, indicating that the dysregulation was mainly occurring at a posttranslational level. The altered expression of liver AQP9 during BDL was not dependent on insulin, a hormone known to negatively regulate AQP9 at a transcriptional level, since insulinemia was unchanged in 7-day BDL rats. Overall, these results suggest that extrahepatic cholestasis leads to downregulation of AQP9 in the hepatocyte basolateral plasma membrane and dysregulated aquaporin channels contribute to bile flow dysfunction of cholestatic hepatocyte.

aquaglyceroporin; water channel; bile; bile duct ligation