Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis

Flavia I. Carreras, Sergio A. Gradilone, Amelia Mazzone, Fabiana García, Bing Q. Huang, J. Elena Ochoa, Pamela S. Tietz, Nicholas F La Russo, Giuseppe Calamita, Raúl A. Marinelli

Research output: Contribution to journalArticle

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Abstract

Hepatocytes express the water channel aquaporin-8 (AQP8), which is mainly localized in intracellular vesicles, and its adenosine 3′,5′-cyclic monophosphate (cAMP)-induced translocation to the plasma membrane facilitates osmotic water movement during canalicular bile secretion. Thus, defective expression of AQP8 may be associated with secretory dysfunction of hepatocytes caused by extrahepatic cholestasis. We studied the effect of 1, 3, and 7 days of bile duct ligation (BDL) on protein expression, subcellular localization, and messenger RNA (mRNA) levels of AQP8; this was determined in rat livers by immunoblotting in subcellular membranes, light immunohistochemistry, immunogold electron microscopy, and Northern blotting. One day of BDL did not affect expression or subcellular localization of AQP8. Three days of BDL reduced the amount of intracellular AQP8 (75%; P < .001) without affecting its plasma membrane expression. Seven days after BDL, AQP8 was markedly decreased in intracellular (67%; P < .05) and plasma (56%; P < .05) membranes. Dibutyryl cAMP failed to increase AQP8 in plasma membranes from liver slices, suggesting a defective translocation of AQP8 in 7-day BDL rats. Immunohistochemistry and immunoelectron microscopy in liver sections confirmed the BDL-induced decreased expression of hepatocyte AQP8 in intracellular vesicles and canalicular membranes. AQP8 mRNA expression was unaffected by 1-day BDL but was significantly increased by about 200% in 3- and 7-day BDL rats, indicating a posttranscriptional mechanism for protein level reduction. In conclusion, BDL-induced extrahepatic cholestasis caused posttranscriptional downregulation of hepatocyte AQP8 protein expression. Defective expression of AQP8 water channels may contribute to bile secretory dysfunction of cholestatic hepatocytes.

Original languageEnglish (US)
Pages (from-to)1026-1033
Number of pages8
JournalHepatology
Volume37
Issue number5
DOIs
StatePublished - May 1 2003

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Extrahepatic Cholestasis
Aquaporins
Hepatocytes
Bile Ducts
Ligation
Cell Membrane
Bile
Membranes
aquaporin 8
Liver
Immunohistochemistry
Water Movements
Messenger RNA
Proteins
Immunoelectron Microscopy
Immunoblotting
Northern Blotting
Adenosine

ASJC Scopus subject areas

  • Hepatology

Cite this

Carreras, F. I., Gradilone, S. A., Mazzone, A., García, F., Huang, B. Q., Ochoa, J. E., ... Marinelli, R. A. (2003). Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. Hepatology, 37(5), 1026-1033. https://doi.org/10.1053/jhep.2003.50170

Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. / Carreras, Flavia I.; Gradilone, Sergio A.; Mazzone, Amelia; García, Fabiana; Huang, Bing Q.; Ochoa, J. Elena; Tietz, Pamela S.; La Russo, Nicholas F; Calamita, Giuseppe; Marinelli, Raúl A.

In: Hepatology, Vol. 37, No. 5, 01.05.2003, p. 1026-1033.

Research output: Contribution to journalArticle

Carreras, FI, Gradilone, SA, Mazzone, A, García, F, Huang, BQ, Ochoa, JE, Tietz, PS, La Russo, NF, Calamita, G & Marinelli, RA 2003, 'Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis', Hepatology, vol. 37, no. 5, pp. 1026-1033. https://doi.org/10.1053/jhep.2003.50170
Carreras FI, Gradilone SA, Mazzone A, García F, Huang BQ, Ochoa JE et al. Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. Hepatology. 2003 May 1;37(5):1026-1033. https://doi.org/10.1053/jhep.2003.50170
Carreras, Flavia I. ; Gradilone, Sergio A. ; Mazzone, Amelia ; García, Fabiana ; Huang, Bing Q. ; Ochoa, J. Elena ; Tietz, Pamela S. ; La Russo, Nicholas F ; Calamita, Giuseppe ; Marinelli, Raúl A. / Rat hepatocyte aquaporin-8 water channels are down-regulated in extrahepatic cholestasis. In: Hepatology. 2003 ; Vol. 37, No. 5. pp. 1026-1033.
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abstract = "Hepatocytes express the water channel aquaporin-8 (AQP8), which is mainly localized in intracellular vesicles, and its adenosine 3′,5′-cyclic monophosphate (cAMP)-induced translocation to the plasma membrane facilitates osmotic water movement during canalicular bile secretion. Thus, defective expression of AQP8 may be associated with secretory dysfunction of hepatocytes caused by extrahepatic cholestasis. We studied the effect of 1, 3, and 7 days of bile duct ligation (BDL) on protein expression, subcellular localization, and messenger RNA (mRNA) levels of AQP8; this was determined in rat livers by immunoblotting in subcellular membranes, light immunohistochemistry, immunogold electron microscopy, and Northern blotting. One day of BDL did not affect expression or subcellular localization of AQP8. Three days of BDL reduced the amount of intracellular AQP8 (75{\%}; P < .001) without affecting its plasma membrane expression. Seven days after BDL, AQP8 was markedly decreased in intracellular (67{\%}; P < .05) and plasma (56{\%}; P < .05) membranes. Dibutyryl cAMP failed to increase AQP8 in plasma membranes from liver slices, suggesting a defective translocation of AQP8 in 7-day BDL rats. Immunohistochemistry and immunoelectron microscopy in liver sections confirmed the BDL-induced decreased expression of hepatocyte AQP8 in intracellular vesicles and canalicular membranes. AQP8 mRNA expression was unaffected by 1-day BDL but was significantly increased by about 200{\%} in 3- and 7-day BDL rats, indicating a posttranscriptional mechanism for protein level reduction. In conclusion, BDL-induced extrahepatic cholestasis caused posttranscriptional downregulation of hepatocyte AQP8 protein expression. Defective expression of AQP8 water channels may contribute to bile secretory dysfunction of cholestatic hepatocytes.",
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AU - Gradilone, Sergio A.

AU - Mazzone, Amelia

AU - García, Fabiana

AU - Huang, Bing Q.

AU - Ochoa, J. Elena

AU - Tietz, Pamela S.

AU - La Russo, Nicholas F

AU - Calamita, Giuseppe

AU - Marinelli, Raúl A.

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