Ethanol-Induced Apoptosis in Mouse Liver
Open accessAbstract
Hepatic apoptosis has been shown to occur in both experimental and clinical alcoholic liver disease, but the signaling pathway remains unknown. This study was undertaken to examine specifically the involvement of the upstream signals, Fas and cytochrome c, in alcohol-induced caspase-3 activation and apoptosis in the liver. Male FVB mice were administrated intragastrically a single dose of alcohol at 6 g/kg, which has been shown to represent binge drinking in humans. Hepatic apoptosis was detected by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Active form of caspase-3 was identified by immunoperoxidase staining and confirmed by immunogold labeling and was found to be in the cytosol and nucleus. Enzymic assay further confirmed caspase-3 activation and nucleus localization. Systemic administration of caspase-3 inhibitor, Ac-DEVD-FMK, inhibited caspase-3 activity and abrogated apoptosis. Elevation of cytosolic cytochrome c was found by immunoperoxidase staining, immunogold labeling, and Western blot. Increased Fas ligand expression was detected by immunoperoxidase staining. Intravenous administration of a neutralizing Fas ligand monoclonal antibody resulted in suppression of caspase-3 activation and attenuation of apoptosis, but did not inhibit mitochondrial cytochrome c release. The results thus demonstrate that Fas/Fas ligand system-mediated caspase-3 activation plays a central role in the ethanol-induced hepatic apoptosis.
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Fas-mediated apoptosis is also reduced, as judged by using the monoclonal antibody Jo2 that recognizes and activates the Fas receptor and induces hepatic apoptosis, or by using ethanol gavage in mice, a system that mimics binge drinking in humans and triggers FasL-induced hepatocyte apoptosis.
“Fas-mediated apoptosis is also reduced, as judged by using the monoclonal antibody Jo2 that recognizes and activates the Fas receptor and induces hepatic apoptosis [109], or by using ethanol gavage in mice, a system that mimics binge drinking in humans and triggers FasL-induced hepatocyte apoptosis [110].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [110]
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Cites
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167 · see citing works
Caspases: the executioners of apoptosis
Cohen, G. M. (1997) · Biochemical Journal · doi:10.1042/bj3260001 · Cited by 4,720 · see citing works
Nagata, S., & Golstein, P. (1995) · Science · doi:10.1126/science.7533326 · Cited by 3,979 · see citing works
Emerging roles of caspase-3 in apoptosis
Porter, A. G., & Jänicke, R. U. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400476 · Cited by 3,870 · see citing works
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881 · see citing works
Mitochondrial control of apoptosis: the role of cytochrome c.
Cai, J.-Y., Yang, J., & Jones, D. P. (1998) · Biochimica et Biophysica Acta · doi:10.1016/s0005-2728(98)00109-1 · Cited by 777 · see citing works
Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.
Galle, P. R., Hofmann, W. J., Walczak, H., Schaller, H., Otto, G., Stremmel, W., Krammer, P. H., & Runkel, L. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1223 · Cited by 692 · see citing works
Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor
Yaoita, H., Ogawa, K., Maehara, K., & Maruyama, Y. (1998) · Circulation · doi:10.1161/01.cir.97.3.276 · Cited by 627 · see citing works
Krajewska, M., Wang, H., Krajewski, S., Zapata, J. M., Shabaik, A. S., Gascoyne, R. D., & Reed, J. C. (1997) · PubMed · Cited by 428 · see citing works
Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells
Faleiro, L. J., Kobayashi, R., Fearnhead, H. O., & Lazebnik, Y. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.9.2271 · Cited by 357 · see citing works
Chandler, J. M., Cohen, G. M., & MacFarlane, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.18.10815 · Cited by 237 · see citing works
Fas-Mediated Apoptosis in Adriamycin-Induced Cardiomyopathy in Rats
Nakamura, T., Ueda, Y., Juan, Y., Katsuda, S., Takahashi, H., & Koh, E. (2000) · Circulation · doi:10.1161/01.cir.102.5.572 · Cited by 226 · see citing works
Cursio, R., Gugenheim, J., Ricci, J., Crénesse, D., Rostagno, P., Maulon, L., Saint‐Paul, M., Ferruà, B., & Auberger, P. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.2.253 · Cited by 219 · see citing works
Oxidative Stress–Mediated Apoptosis of Hepatocytes Exposed to Acute Ethanol Intoxication
Kurose, I., Higuchi, H., Miura, S., et al. (1997) · Hepatology · doi:10.1002/hep.510250219 · Cited by 219 · see citing works
Halsted, C. H., Villanueva, J. A., Chandler, C. J., et al. (1996) · Hepatology · doi:10.1002/hep.510230314 · Cited by 177 · see citing works
Carson, E. J., & Pruett, S. B. (1996) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1996.tb01055.x · Cited by 167 · see citing works
Buckley, A. R., Crowe, P. D., & Russell, D. H. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.22.8649 · Cited by 147 · see citing works
Bajt, M. L. (2000) · Toxicological Sciences · doi:10.1093/toxsci/58.1.109 · Cited by 135 · see citing works
Leist, M., Gantner, F., Künstle, G., Bohlinger, I., Tiegs, G., Bluethmann, H., & Wendel, A. (1996) · Molecular Medicine · doi:10.1007/bf03402207 · Cited by 126 · see citing works
Zhang, F. X., Rubin, R., & Rooney, T. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71010196.x · Cited by 125 · see citing works
Apoptosis in the Absence of Cytochrome c Accumulation in the Cytosol
Tang, D. G., Li, L., Zhu, Z., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7969 · Cited by 116 · see citing works
Apoptosis and Alcoholic Liver Disease
Nanji, A. A. (1998) · Seminars in Liver Disease · doi:10.1055/s-2007-1007154 · Cited by 104 · see citing works
Goldin, R. D., Hunt, N. C. A., Clark, J., & Wickramasinghe, S. N. (1993) · The Journal of Pathology · doi:10.1002/path.1711710115 · Cited by 100 · see citing works
Deaciuc, I. V., Fortunato, F., D'Souza, N. B., et al. (1999) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1999.tb04121.x · Cited by 100 · see citing works
Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases
Jones, R. A., Johnson, V., Buck, N. R., Dobrota, M., Hinton, R. H., Chow, S. C., & Kass, G. E. N. (1998) · Hepatology · doi:10.1002/hep.510270624 · Cited by 91 · see citing works
Subcellular changes and apoptosis induced by ethanol in rat liver
Benedetti, A., Brunelli, E., Risicato, R., Cilluffo, T., Jézéquel, A. M., & Orlandi, F. (1988) · Journal of Hepatology · doi:10.1016/s0168-8278(88)80024-2 · Cited by 86 · see citing works
Chronic ethanol feeding increases apoptosis and cell proliferation in rat liver
Svegliati‐Baroni, G., Marucci, L., Benedetti, A., et al. (1994) · Journal of Hepatology · doi:10.1016/s0168-8278(05)80498-2 · Cited by 82 · see citing works
Apoptosis and Bcl‐2 Protein Expression in Experimental Alcoholic Liver Disease in the Rat
Yacoub, L. K., Fogt, F., Griniuvienė, B., et al. (1995) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb00958.x · Cited by 81 · see citing works
The apoptotic cysteine protease CPP32
Kumar, S. (1997) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(96)00146-x · Cited by 75 · see citing works
Farber, A. M., Connors, J. P., Friedlander, R. M., Wagner, R. J., Powell, R. J., & Cronenwett, J. L. (1999) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(99)70115-1 · Cited by 63 · see citing works
Mi, L., Mak, K. M., & Lieber, C. S. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb04592.x · Cited by 58 · see citing works
Gastric mucosal apoptosis induced by ethanol: effect of antiulcer agents
Piotrowski, J., Piotrowski, E., Skrodzka, D., Slomiany, A., & Slomiany, B. L. (1997) · IUBMB Life · doi:10.1080/15216549700202631 · Cited by 52 · see citing works
Collier, S. D., Wu, W., & Pruett, S. B. (1998) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1997.8324 · Cited by 48 · see citing works
Alcohol-induced thymocyte apoptosis is accompanied by impaired mitochondrial function
Wang, J., & Spitzer, J. J. (1997) · Alcohol · doi:10.1016/s0741-8329(97)86148-4 · Cited by 44 · see citing works
Slomiany, B. L., Piotrowski, J., & Slomiany, A. (1997) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-199711000-00025 · Cited by 43 · see citing works
TUNEL-positive hepatocytes in alcoholic liver disease
Zhao, M., Laissue, J. A., & Zimmermann, A. (1997) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280050108 · Cited by 40 · see citing works
Suarez‐Pinzon, W. L., Power, R. F., & Rabinovitch, A. (2000) · Diabetologia · doi:10.1007/s001250051506 · Cited by 39 · see citing works
Induction of buccal mucosal apoptosis with chronic alcohol ingestion
Slomiany, B. L., Piotrowski, J., Piotrowski, E., et al. (1998) · IUBMB Life · doi:10.1080/15216549800201392 · Cited by 24 · see citing works
Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases
Jiang, Z., Liu, Y., Savas, L., et al. (1997) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280050087 · Cited by 20 · see citing works
Slomiany, A., Piotrowski, E. R., Grabska, M., et al. (1999) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1999.tb04119.x · Cited by 19 · see citing works
Slomiany, B. L., Piotrowski, J., Piotrowski, E., et al. (1998) · IUBMB Life · doi:10.1080/15216549800203432 · Cited by 9 · see citing works
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Research works printed but not linked: 1
- Deuciuc IV, Fortunato F, D'Souza NB, Hill DB, Schmidt J, Lee EY, McClain CJ: Modulation of caspase-3 activity and Fas ligand mRNA expression in rat liver cells in vivo by alcohol and lipopolysaccharide. Alcohol Clin Exp Res 1999, 23:349 -356
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Ding, W., Li, M., Chen, X., Ni, H., Lin, C., Gao, W., Lu, B., Stolz, D. B., Clemens, D. L., & Yin, X. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.07.041 · Cited by 515 · see citing works
CCN1/CYR61: the very model of a modern matricellular protein
Lau, L. F. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0778-3 · Cited by 338 · see citing works
Alcoholic liver disease: pathogenesis and new targets for therapy
Altamirano, J., & Bataller, R. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2011.134 · Cited by 284 · see citing works
CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis
Abdelmegeed, M. A., Banerjee, A., Jang, S., Yoo, S.-H., Yun, J.-W., Gonzalez, F. J., Keshavarzian, A., & Song, B.-J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.009 · Cited by 191 · see citing works
Juric, V., Chen, C.-C., & Lau, L. F. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00064-09 · Cited by 70 · see citing works
Chen, C., & Lau, L. F. (2010) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-009-0080-4 · Cited by 47 · see citing works
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- Authors
- Zhou, Z., Sun, X., & Kang, Y. J.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Kang, Y. James
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 159
- Issue
- 1
- Pages
- 329-338
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1850406
- OpenAlex
- W2147525297
- Cited by
- 129
- References
- 41
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 6 · 2013: 6 · 2012: 5
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R21AA013601)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- ethanol-induced apoptosis, alcoholic liver disease, Fas/Fas ligand pathway, caspase-3 activation, cytochrome c release, mitochondrial apoptosis, binge drinking, liver
- MeSH terms
- Ethanol, Animals, Antibodies, Monoclonal, Cytochrome c Group, Enzyme Activation, Liver, Male, Membrane Glycoproteins, Oligopeptides, Time Factors, Tissue Distribution, Cysteine Proteinase Inhibitors, Apoptosis, Caspases, Mice, Caspase 3, Fas Ligand Protein, Caspase Inhibitors
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