| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905
Toxic bile salts induce hepatocyte apoptosis by a Fas-dependent, Fas ligand-independent mechanism. To account for this observation, we formulated the hypothesis that toxic bile salts induce apoptosis by effecting translocation of cytoplasmic Fas to the cell surface, resulting in transduction of Fas death signals. In McNtcp.24 cells the majority of Fas was cytoplasmic, as assessed by cell fractionation and immunofluorescence studies. However, cell surface Fas increased sixfold after treatment with the toxic bile salt glycochenodeoxycholate (GCDC) in the absence of increased Fas protein expression. Moreover, in cells transfected with Fas-green fluorescence protein, cell surface fluorescence also increased in GCDC-treated cells, directly demonstrating Fas translocation to the plasma membrane. Both brefeldin A, a Golgi-disrupting agent, and nocodazole, a microtubule inhibitor, prevented the GCDC-induced increase in cell surface Fas and apoptosis. In conclusion, toxic bile salts appear to induce apoptosis by promoting cytoplasmic transport of Fas to the cell surface by a Golgi- and microtubule-dependent pathway.
brefeldin A; Fas-green fluorescence protein; JO-2 antisera; nocodazole; vesicle trafficking
This article has been cited by other articles:
|
|
 |
|
  C Rust, K Bauchmuller, C Bernt, T Vennegeerts, P Fickert, A Fuchsbichler, and U Beuers Sulfasalazine reduces bile acid induced apoptosis in human hepatoma cells and perfused rat livers Gut, May 1, 2006; 55(5): 719 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yui, T. Saeki, R. Kanamoto, and K. Iwami Characteristics of Apoptosis in HCT116 Colon Cancer Cells Induced by Deoxycholic Acid J. Biochem., August 1, 2005; 138(2): 151 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M E Guicciardi and G J Gores Apoptosis: a mechanism of acute and chronic liver injury Gut, July 1, 2005; 54(7): 1024 - 1033. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wang, J. J. Brems, R. L. Gamelli, and J. Ding Reversibility of Caspase Activation and Its Role during Glycochenodeoxycholate-induced Hepatocyte Apoptosis J. Biol. Chem., June 24, 2005; 280(25): 23490 - 23495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Cullen Mechanistic Classification of Liver Injury Toxicol Pathol, January 1, 2005; 33(1): 6 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Rolo, C. M. Palmeira, J. M. Holy, and K. B. Wallace Role of Mitochondrial Dysfunction in Combined Bile Acid-Induced Cytotoxicity: The Switch Between Apoptosis and Necrosis Toxicol. Sci., May 1, 2004; 79(1): 196 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Qiao, S. I. Han, Y. Fang, J. S. Park, S. Gupta, D. Gilfor, G. Amorino, K. Valerie, L. Sealy, J. F. Engelhardt, et al. Bile Acid Regulation of C/EBP{beta}, CREB, and c-Jun Function, via the Extracellular Signal-Regulated Kinase and c-Jun NH2-Terminal Kinase Pathways, Modulates the Apoptotic Response of Hepatocytes Mol. Cell. Biol., May 1, 2003; 23(9): 3052 - 3066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Higuchi and G. J. Gores Bile Acid Regulation of Hepatic Physiology: IV. Bile acids and death receptors Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G734 - G738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Higuchi, J.-H. Yoon, A. Grambihler, N. Werneburg, S. F. Bronk, and G. J. Gores Bile Acids Stimulate cFLIP Phosphorylation Enhancing TRAIL-mediated Apoptosis J. Biol. Chem., January 3, 2003; 278(1): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Barrett, F. L. Lewis, J. B. Roaten, T. W. Sweatman, M. Israel, J. L. Cleveland, and L. Lothstein Novel Extranuclear-targeted Anthracyclines Override the Antiapoptotic Functions of Bcl-2 and Target Protein Kinase C Pathways to Induce Apoptosis Mol. Cancer Ther., May 1, 2002; 1(7): 469 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jaeschke, G. J. Gores, A. I. Cederbaum, J. A. Hinson, D. Pessayre, and J. J. Lemasters Mechanisms of Hepatotoxicity Toxicol. Sci., February 1, 2002; 65(2): 166 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Higuchi, H. Miyoshi, S. F. Bronk, H. Zhang, N. Dean, and G. J. Gores Bid Antisense Attenuates Bile Acid-Induced Apoptosis and Cholestatic Liver Injury J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 866 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hatano and D. A. Brenner Akt protects mouse hepatocytes from TNF-alpha - and Fas-mediated apoptosis through NK-kappa B activation Am J Physiol Gastrointest Liver Physiol, December 1, 2001; 281(6): G1357 - G1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Higuchi, S. F. Bronk, Y. Takikawa, N. Werneburg, R. Takimoto, W. El-Deiry, and G. J. Gores The Bile Acid Glycochenodeoxycholate Induces TRAIL-Receptor 2/DR5 Expression and Apoptosis J. Biol. Chem., October 12, 2001; 276(42): 38610 - 38618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M ARRESE and S J KARPEN New horizons in the regulation of bile acid and lipid homeostasis: critical role of the nuclear receptor FXR as an intracellular bile acid sensor Gut, October 1, 2001; 49(4): 465 - 466. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Qiao, E. Studer, K. Leach, R. McKinstry, S. Gupta, R. Decker, R. Kukreja, K. Valerie, P. Nagarkatti, W. E. Deiry, et al. Deoxycholic Acid (DCA) Causes Ligand-independent Activation of Epidermal Growth Factor Receptor (EGFR) and FAS Receptor in Primary Hepatocytes: Inhibition of EGFR/Mitogen-activated Protein Kinase-Signaling Module Enhances DCA-induced Apoptosis Mol. Biol. Cell, September 1, 2001; 12(9): 2629 - 2645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gilbert, A. Loranger, N. Daigle, and N. Marceau Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation J. Cell Biol., August 20, 2001; 154(4): 763 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wang, M. Salem, I. M. Yousef, B. Tuchweber, P. Lam, S. J. Childs, C. D. Helgason, C. Ackerley, M. J. Phillips, and V. Ling Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis PNAS, February 1, 2001; (2001) 31465498. [Abstract] [Full Text]
|
|
|
|
|
|
R. Wang, M. Salem, I. M. Yousef, B. Tuchweber, P. Lam, S. J. Childs, C. D. Helgason, C. Ackerley, M. J. Phillips, and V. Ling Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis PNAS, February 13, 2001; 98(4): 2011 - 2016. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
