HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reiners, J. J. Articles by Clift, R. E. Search for Related Content PubMed PubMed Citation Articles by Reiners, J. J., Jr. Articles by Clift, R. E. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 4, 2502-2510, January 22, 1999

Aryl Hydrocarbon Receptor Regulation of Ceramide-induced Apoptosis in Murine Hepatoma 1c1c7 Cells
A FUNCTION INDEPENDENT OF ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR

From the Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201

The relationship between aryl hydrocarbon receptor (AHR) content and susceptibility to apoptosis was examined in the murine hepatoma 1c1c7 cell line and a series of variants having different levels of AHR expression. Exposure of 1c1c7 cultures to N-acetylsphingosine (C₂-ceramide) caused a concentration-dependent inhibition of cell proliferation, loss of viability, and induction of apoptosis as monitored by analyses of DNA fragmentation and caspase activation. A variant cell line (Tao) having ~10% of the AHR content of 1c1c7 cells also arrested following exposure to C₂-ceramide, but did not undergo apoptosis. Modulation of 1c1c7 and Tao AHR contents by transfection of Ahr antisense and sense constructs, respectively, confirmed the relationship between AHR content and susceptibility to C₂-ceramide-induced apoptosis. C₂-ceramide also induced the apoptosis of an AHR-containing cell line lacking the aryl hydrocarbon receptor nuclear translocator protein. AHR ligands (i.e. 2,3,7,8-tetrachlorodibenzo-p-dioxin and -naphthoflavone) neither induced apoptosis nor modulated the development of apoptosis in C₂-ceramide-treated 1c1c7 cultures. AHR content did not affect staurosporine- or doxorubicin-induced apoptosis. These results suggest the AHR modulates aspects of ceramide signaling associated with the induction of apoptosis but not cell cycle arrest, and does so by a mechanism that is independent of its interaction with aryl hydrocarbon receptor nuclear translocator and exogenous AHR ligands.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				G. Biswas, S. Srinivasan, H. K. Anandatheerthavarada, and N. G. Avadhani Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling PNAS, January 8, 2008; 105(1): 186 - 191. [Abstract] [Full Text] [PDF]

				R. Wu, L. Zhang, M. S. Hoagland, and H. I. Swanson Lack of the Aryl Hydrocarbon Receptor Leads to Impaired Activation of AKT/Protein Kinase B and Enhanced Sensitivity to Apoptosis Induced via the Intrinsic Pathway J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 448 - 457. [Abstract] [Full Text] [PDF]

				J. A. Caruso, P. A. Mathieu, A. Joiakim, H. Zhang, and J. J. Reiners Jr. Aryl Hydrocarbon Receptor Modulation of Tumor Necrosis Factor-{alpha}-induced Apoptosis and Lysosomal Disruption in a Hepatoma Model That Is Caspase-8-independent J. Biol. Chem., April 21, 2006; 281(16): 10954 - 10967. [Abstract] [Full Text] [PDF]

				P. Pocar, D. Nestler, M. Risch, and B. Fischer Apoptosis in bovine cumulus-oocyte complexes after exposure to polychlorinated biphenyl mixtures during in vitro maturation Reproduction, December 1, 2005; 130(6): 857 - 868. [Abstract] [Full Text] [PDF]

				P Pocar, B Fischer, T Klonisch, and S Hombach-Klonisch Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction Reproduction, April 1, 2005; 129(4): 379 - 389. [Abstract] [Full Text] [PDF]

				K.-T. Park, K. A. Mitchell, G. Huang, and C. J. Elferink The Aryl Hydrocarbon Receptor Predisposes Hepatocytes to Fas-Mediated Apoptosis Mol. Pharmacol., March 1, 2005; 67(3): 612 - 622. [Abstract] [Full Text] [PDF]

				A. Joiakim, P. A. Mathieu, A. A. Elliott, and J. J. Reiners Jr. Superinduction of CYP1A1 in MCF10A Cultures by Cycloheximide, Anisomycin, and Puromycin: A Process Independent of Effects on Protein Translation and Unrelated to Suppression of Aryl Hydrocarbon Receptor Proteolysis by the Proteasome Mol. Pharmacol., October 1, 2004; 66(4): 936 - 947. [Abstract] [Full Text] [PDF]

				J. A. Walisser, M. K. Bunger, E. Glover, E. B. Harstad, and C. A. Bradfield Patent Ductus Venosus and Dioxin Resistance in Mice Harboring a Hypomorphic Arnt Allele J. Biol. Chem., April 16, 2004; 279(16): 16326 - 16331. [Abstract] [Full Text] [PDF]

				J. A. Caruso, P. A. Mathieu, A. Joiakim, B. Leeson, D. Kessel, B. F. Sloane, and J. J. Reiners Jr. Differential Susceptibilities of Murine Hepatoma 1c1c7 and Tao Cells to the Lysosomal Photosensitizer NPe6: Influence of Aryl Hydrocarbon Receptor on Lysosomal Fragility and Protease Contents Mol. Pharmacol., April 1, 2004; 65(4): 1016 - 1028. [Abstract] [Full Text]

				M. K. Bunger, S. M. Moran, E. Glover, T. L. Thomae, G. P. Lahvis, B. C. Lin, and C. A. Bradfield Resistance to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicity and Abnormal Liver Development in Mice Carrying a Mutation in the Nuclear Localization Sequence of the Aryl Hydrocarbon Receptor J. Biol. Chem., May 9, 2003; 278(20): 17767 - 17774. [Abstract] [Full Text] [PDF]

				R. R. Mattingly, R. A. Gibbs, R. E. Menard, and J. J. Reiners Jr. Potent Suppression of Proliferation of A10 Vascular Smooth Muscle Cells by Combined Treatment with Lovastatin and 3-Allylfarnesol, an Inhibitor of Protein Farnesyltransferase J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 74 - 81. [Abstract] [Full Text] [PDF]

				J. M. Seubert, A. J. Darmon, A. O. S. El-Kadi, S. J. A. D'Souza, and J. R. Bend Apoptosis in Murine Hepatoma Hepa 1c1c7 Wild-Type, C12, and C4 Cells Mediated by Bilirubin Mol. Pharmacol., August 1, 2002; 62(2): 257 - 264. [Abstract] [Full Text] [PDF]

				R. P. Santini, S. Myrand, C. Elferink, and J. J. Reiners Jr. Regulation of Cyp1a1 Induction by Dioxin as a Function of Cell Cycle Phase J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 718 - 728. [Abstract] [Full Text] [PDF]

				D. Kessel, J. A. Caruso, and J. J. Reiners Jr. Potentiation of Photodynamic Therapy by Ursodeoxycholic Acid Cancer Res., December 1, 2000; 60(24): 6985 - 6988. [Abstract] [Full Text]

				B. PAIGEN, N. J. SCHORK, K. L. SVENSON, Y.-C. CHEAH, J.-L. MU, F. LAMMERT, D. Q.-H. WANG, G. BOUCHARD, and M. C. CAREY Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice Physiol Genomics, November 9, 2000; 4(1): 59 - 65. [Abstract] [Full Text] [PDF]

				S. A. Quadri, A. N. Qadri, M. E. Hahn, K. K. Mann, and D. H. Sherr The Bioflavonoid Galangin Blocks Aryl Hydrocarbon Receptor Activation and Polycyclic Aromatic Hydrocarbon-Induced Pre-B Cell Apoptosis Mol. Pharmacol., September 1, 2000; 58(3): 515 - 525. [Abstract] [Full Text]

				Q. Ma, A. J. Renzelli, K. T. Baldwin, and J. M. Antonini Superinduction of CYP1A1 Gene Expression. REGULATION OF 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN-INDUCED DEGRADATION OF Ah RECEPTOR BY CYCLOHEXIMIDE J. Biol. Chem., April 21, 2000; 275(17): 12676 - 12683. [Abstract] [Full Text] [PDF]

				Q. Ma and K. T. Baldwin 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Degradation of Aryl Hydrocarbon Receptor (AhR) by the Ubiquitin-Proteasome Pathway. ROLE OF THE TRANSCRIPTION ACTIVATON AND DNA BINDING OF AhR J. Biol. Chem., March 17, 2000; 275(12): 8432 - 8438. [Abstract] [Full Text] [PDF]

				A. Puga, S. J. Barnes, T. P. Dalton, C.-y. Chang, E. S. Knudsen, and M. A. Maier Aromatic Hydrocarbon Receptor Interaction with the Retinoblastoma Protein Potentiates Repression of E2F-dependent Transcription and Cell Cycle Arrest J. Biol. Chem., January 28, 2000; 275(4): 2943 - 2950. [Abstract] [Full Text] [PDF]