ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins

R. Brian Doctor, Rolf H. Dahl, Kelli D. Salter, Laura Fouassier, Jing Chen, J. Gregory Fitz

Research output: Contribution to journalArticle

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Abstract

Intrahepatic bile ducts (BD) are a critical target of injury in the postischemic liver. Decreased vascular perfusion causes characteristic changes in the morphology of the ductular epithelia including a loss of secondary membrane structures and a decrease in plasma membrane surface area. Using adenosine triphosphate (ATP) depletion of cultured normal rat cholangiocytes (NRC) to model ischemic ducts, the present studies examined the fate of apical membrane proteins to determine whether membrane recycling might contribute to rapid functional recovery. Apical proteins, including γ- glutamyl transpeptidase (GGT), Na+-glucose cotransporter (SGLT1), and apically biotinylated proteins, were not shed into the luminal space during ATP depletion. Instead, labeling of surface proteins after ATP depletion showed a significant decrease in GGT and SGLT1, consistent with membrane internalization. Similarly, z-axis confocal microscopy of biotinylated apical proteins also showed protein internalization. During ATP recovery, SGLT1 transport activity remained profoundly depressed even after 24 hours of recovery, indicating that the function of the internalized apical proteins is not rapidly recovered. These studies suggest that the membrane internalization in ATP-depleted cholangiocytes is a unidirectional process that contributes to prolonged functional deficits after restoration of normal cellular ATP levels. This sustained decrease in transport capacity may contribute to the development of ductular injury in postischemic livers.

Original languageEnglish (US)
Pages (from-to)1045-1054
Number of pages10
JournalHepatology
Volume31
Issue number5
StatePublished - 2000

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Membrane Proteins
Adenosine Triphosphate
Membranes
Proteins
Intrahepatic Bile Ducts
gamma-Glutamyltransferase
Liver
Recovery of Function
Wounds and Injuries
Confocal Microscopy
Blood Vessels
Epithelium
Perfusion
Cell Membrane
Glucose

ASJC Scopus subject areas

  • Hepatology

Cite this

Doctor, R. B., Dahl, R. H., Salter, K. D., Fouassier, L., Chen, J., & Fitz, J. G. (2000). ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins. Hepatology, 31(5), 1045-1054.

ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins. / Doctor, R. Brian; Dahl, Rolf H.; Salter, Kelli D.; Fouassier, Laura; Chen, Jing; Fitz, J. Gregory.

In: Hepatology, Vol. 31, No. 5, 2000, p. 1045-1054.

Research output: Contribution to journalArticle

Doctor, RB, Dahl, RH, Salter, KD, Fouassier, L, Chen, J & Fitz, JG 2000, 'ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins', Hepatology, vol. 31, no. 5, pp. 1045-1054.
Doctor RB, Dahl RH, Salter KD, Fouassier L, Chen J, Fitz JG. ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins. Hepatology. 2000;31(5):1045-1054.
Doctor, R. Brian ; Dahl, Rolf H. ; Salter, Kelli D. ; Fouassier, Laura ; Chen, Jing ; Fitz, J. Gregory. / ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins. In: Hepatology. 2000 ; Vol. 31, No. 5. pp. 1045-1054.
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