Effects of minocycline on Fas-mediated fulminant hepatitis in mice

Heng-Cheng Chu, Yi-Ling Lin, Huey-Kang Sytwu, Shin-Hua Lin, Ching-Len Liao, You-Chen Chao

研究成果: 雜誌貢獻文章

19 引文 (Scopus)

摘要

Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. Intraperitoneal injection of Jo2 (0.6 μg g -1) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg -1) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.
原文英語
頁(從 - 到)275-282
頁數8
期刊British Journal of Pharmacology
144
發行號2
DOIs
出版狀態已發佈 - 2005
對外發佈Yes

指紋

Minocycline
Hepatitis
Caspases
Cytochromes c
Liver
Liver Extracts
Caspase 8
Liver Mitochondrion
Aspartate Aminotransferases
Intraperitoneal Injections
Alanine Transaminase
Inbred C57BL Mouse
Caspase 3
Cartilage
Liver Diseases
Anti-Idiotypic Antibodies
Anti-Inflammatory Agents
Neurons

引用此文

Effects of minocycline on Fas-mediated fulminant hepatitis in mice. / Chu, Heng-Cheng; Lin, Yi-Ling; Sytwu, Huey-Kang; Lin, Shin-Hua; Liao, Ching-Len; Chao, You-Chen.

於: British Journal of Pharmacology, 卷 144, 編號 2, 2005, p. 275-282.

研究成果: 雜誌貢獻文章

Chu, H-C, Lin, Y-L, Sytwu, H-K, Lin, S-H, Liao, C-L & Chao, Y-C 2005, 'Effects of minocycline on Fas-mediated fulminant hepatitis in mice', British Journal of Pharmacology, 卷 144, 編號 2, 頁 275-282. https://doi.org/10.1038/sj.bjp.0706079
Chu, Heng-Cheng ; Lin, Yi-Ling ; Sytwu, Huey-Kang ; Lin, Shin-Hua ; Liao, Ching-Len ; Chao, You-Chen. / Effects of minocycline on Fas-mediated fulminant hepatitis in mice. 於: British Journal of Pharmacology. 2005 ; 卷 144, 編號 2. 頁 275-282.
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title = "Effects of minocycline on Fas-mediated fulminant hepatitis in mice",
abstract = "Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. Intraperitoneal injection of Jo2 (0.6 μg g -1) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg -1) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.",
keywords = "Caspase, Cytochrome c, Fas, Fulminant hepatitis, Minocycline, Mitochondria, caspase 3, caspase 9, cytochrome c, Fas antibody, Fas antigen, jo2 antibody, liver extract, minocycline, protein Bid, unclassified drug, alanine aminotransferase blood level, animal experiment, animal model, animal tissue, antiinflammatory activity, apoptosis, article, aspartate aminotransferase blood level, controlled study, disease model, drug effect, enzyme activation, enzyme release, hepatitis, histopathology, kinetics, liver mitochondrion, male, mouse, mouse strain, nonhuman, priority journal, survival, Animals, Antibodies, Monoclonal, Antigens, CD95, Dose-Response Relationship, Drug, Liver, Liver Failure, Acute, Male, Mice, Mice, Inbred C57BL, Receptors, Tumor Necrosis Factor",
author = "Heng-Cheng Chu and Yi-Ling Lin and Huey-Kang Sytwu and Shin-Hua Lin and Ching-Len Liao and You-Chen Chao",
note = "被引用次數:18 Export Date: 22 March 2016 CODEN: BJPCB 通訊地址: Liao, C.-L.161, Sec. 6, Min-Chuan E Road, Neihu, Taipei 114, Taiwan; 電子郵件: chinglen@ms1.hinet.net 化學物質/CAS: caspase 3, 169592-56-7; caspase 9, 180189-96-2; cytochrome c, 9007-43-6, 9064-84-0; liver extract, 72980-85-9; minocycline, 10118-90-8, 11006-27-2, 13614-98-7; protein Bid, 260235-79-8; Antibodies, Monoclonal; Antigens, CD95; Fas protein, mouse; Minocycline, 10118-90-8; Receptors, Tumor Necrosis Factor; anti-Fas monoclonal antibody 參考文獻: Amin, A.R., Attur, M.G., Thakker, G.D., Patel, P.D., Vyas, P.R., Patel, R.N., Patel, I.R., Abramson, S.B., A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases (1996) Proc. Natl. Acad. Sci. U.S.A., 93, pp. 14014-14019; Ashkenazi, A., Dixit, V.M., Death receptors: Signaling and modulation (1998) Science, 281, pp. 1305-1308; Atillasoy, E., Berk, P.D., Fulminant hepatic failure: Pathophysiology, treatment, and survival (1995) Annu. Rev. Med., 46, pp. 181-191; Bajt, M.L., Lawson, J.A., Vonderfecht, S.L., Gujral, J.S., Jaeschke, H., Protection against Fas receptor-mediated apoptosis in hepatocytes and nonparenchymal cells by a caspase-8 inhibitor in vivo: Evidence for a postmitochondrial processing of caspase-8 (2000) Toxicol. Sci., 58, pp. 109-117; Bocker, R., Estler, C.J., Ludewig-Sandig, D., Evaluation of the hepatotoxic potential of minocycline (1991) Antimicrob. Agents Chemother., 35, pp. 1434-1436; Chang, B., Nishikawa, M., Sato, E., Inoue, M., Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis (2003) Arch. Biochem. Biophys., 411, pp. 63-72; Chen, M., Ona, V.O., Li, M., Ferrante, R.J., Fink, K.B., Zhu, S., Bian, J., Friedlander, R.M., Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease (2000) Nat. Med., 6, pp. 797-801; Du, Y., Ma, Z., Lin, S., Dodel, R.C., Gao, F., Bales, K.R., Triarhou, L.C., Paul, S.M., Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease (2001) Proc. Natl. Acad. Sci. U.S.A., 98, pp. 14669-14674; Feldmann, G., Haouzi, D., Moreau, A., Durand-Schneider, A.M., Bringuier, A., Berson, A., Mansouri, A., Pessayre, D., Opening of the mitochondrial permeability transition pore causes matrix expansion and outer membrane rupture in Fas-mediated hepatic apoptosis in mice (2000) Hepatology, 31, pp. 674-683; Galle, P.R., Hofmann, W.J., Walczak, H., Schaller, H., Otto, G., Stremmel, W., Krammer, P.H., Runkel, L., Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage (1995) J. Exp. Med., 182, pp. 1223-1230; Golub, L.M., Goodson, J.M., Lee, H.M., Vidal, A.M., McNamara, T.F., Ramamurthy, N.S., Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems (1985) J. Periodontol., 56, pp. 93-97; Gough, A., Chapman, S., Wagstaff, K., Emery, P., Elias, E., Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome (1996) BMJ, 312, pp. 169-172; Green, D.R., Reed, J.C., Mitochondria and apoptosis (1998) Science, 281, pp. 1309-1312; Klein, N.C., Cunha, B.A., Tetracyclines (1995) Med. Clin. N. Am., 79, pp. 789-801; Lacronique, V., Mignon, A., Fabre, M., Viollet, B., Rouquet, N., Molina, T., Porteu, A., Kahn, A., Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice (1996) Nat. Med., 2, pp. 80-86; Lawrenson, R.A., Seaman, H.E., Sundstrom, A., Williams, T.J., Farmer, R.D., Liver damage associated with minocycline use in acne: A systematic review of the published literature and pharmacovigilance data (2000) Drug Saf., 23, pp. 333-349; Li, H., Zhu, H., Xu, C.J., Yuan, J., Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis (1998) Cell, 94, pp. 491-501; Lin, S., Wei, X., Xu, Y., Yan, C., Dodel, R., Zhang, Y., Liu, J., Du, Y., Minocycline blocks 6-hydroxydopamine-induced neurotoxicity and free radical production in rat cerebellar granule neurons (2003) Life Sci., 72, pp. 1635-1641; Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., Wang, X., Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade (1997) Cell, 91, pp. 479-489; Luo, X., Budihardjo, I., Zou, H., Slaughter, C., Wang, X., Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors (1998) Cell, 94, pp. 481-490; Malassagne, B., Ferret, P.J., Hammoud, R., Tulliez, M., Bedda, S., Trebeden, H., Jaffray, P., Batteux, F., The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse (2001) Gastroenterology, 121, pp. 1451-1459; Malcolm, A., Heap, T.R., Eckstein, R.P., Lunzer, M.R., Minocycline-induced liver injury (1996) Am. J. Gastroenterol., 91, pp. 1641-1643; Miyachi, Y., Yoshioka, A., Imamura, S., Niwa, Y., Effect of antibiotics on the generation of reactive oxygen species (1986) J. Invest. Dermatol., 86, pp. 449-453; Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Nagata, S., Lethal effect of the anti-Fas antibody in mice (1993) Nature, 364, pp. 806-809; Okamoto, T., The protective effect of glycyrrhizin on anti-Fas antibody-induced hepatitis in mice (2000) Eur. J. Pharmacol., 387, pp. 229-232; Okamoto, T., Hitomi, Y., Hara, A., The protective effect of cyclosporine A on anti-Fas antibody-induced hepatitis in mice (1999) Jpn. J. Pharmacol., 79, pp. 485-488; Okamoto, T., Kawasaki, T., Hino, O., Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway (2003) Biochem. Pharmacol., 65, pp. 677-681; Okamoto, T., Okabe, S., Inhibition of anti-Fas antibody-induced hepatitis by aminoguanidine in mice (2000) Eur. J. Pharmacol., 403, pp. 277-280; Peter, M.E., Krammer, P.H., Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis (1998) Curr. Opin. Immunol., 10, pp. 545-551; Rodriguez, I., Matsuura, K., Khatib, K., Reed, J.C., Nagata, S., Vassalli, P., A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection (1996) J. Exp. Med., 183, pp. 1031-1036; Rodriguez, I., Matsuura, K., Ody, C., Nagata, S., Vassalli, P., Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death (1996) J. Exp. Med., 184, pp. 2067-2072; Sadowski, T., Steinmeyer, J., Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes (2001) J. Rheumatol., 28, pp. 336-340; Sanchez Mejia, R.O., Ona, V.O., Li, M., Friedlander, R.M., Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction (2001) Neurosurgery, 48, pp. 1393-1399. , discussion 1399-1401; Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K.J., Debatin, K.M., Peter, M.E., Two CD95 (APO-1/Fas) signaling pathways (1998) EMBO J., 17, pp. 1675-1687; Scaffidi, C., Schmitz, I., Zha, J., Korsmeyer, S.J., Krammer, P.H., Peter, M.E., Differential modulation of apoptosis sensitivity in CD95 type I and type II cells (1999) J. Biol. Chem., 274, pp. 22532-22538; Seino, K., Setoguchi, Y., Ogino, T., Kayagaki, N., Akiba, H., Nakano, H., Taniguchi, H., Fukao, K., Protection against Fas-mediated and tumor necrosis factor receptor 1-mediated liver injury by blockade of FADD without loss of nuclear factor-kappaB activation (2001) Ann. Surg., 234, pp. 681-688; Song, E., Lee, S.K., Wang, J., Ince, N., Ouyang, N., Min, J., Chen, J., Lieberman, J., RNA interference targeting Fas protects mice from fulminant hepatitis (2003) Nat. Med., 9, pp. 347-351; Strand, S., Hofmann, W.J., Grambihler, A., Hug, H., Volkmann, M., Otto, G., Wesch, H., Galle, P.R., Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis (1998) Nat. Med., 4, pp. 588-593; Tilley, B.C., Alarcon, G.S., Heyse, S.P., Trentham, D.E., Neuner, R., Kaplan, D.A., Clegg, D.O., Fowler, S.E., Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial (1995) Ann. Intern. Med., 122, pp. 81-89. , MIRA Trial Group; Woo, M., Hakem, A., Elia, A.J., Hakem, R., Duncan, G.S., Patterson, B.J., Mak, T.W., In vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes (1999) J. Immunol., 163, pp. 4909-4916; Yamamoto, M., Miura, N., Ohtake, N., Amagaya, S., Ishige, A., Sasaki, H., Komatsu, Y., Terasawa, K., Genipin, a metabolite derived from the herbal medicine Inchin-ko-to, and suppression of Fas-induced lethal liver apoptosis in mice (2000) Gastroenterology, 118, pp. 380-389; Yin, X.M., Wang, K., Gross, A., Zhao, Y., Zinkel, S., Klocke, B., Roth, K.A., Korsmeyer, S.J., Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis (1999) Nature, 400, pp. 886-891; Yrjanheikki, J., Keinanen, R., Pellikka, M., Hokfelt, T., Koistinaho, J., Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia (1998) Proc. Natl. Acad. Sci. U.S.A., 95, pp. 15769-15774; Yrjanheikki, J., Tikka, T., Keinanen, R., Goldsteins, G., Chan, P.H., Koistinaho, J., A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window (1999) Proc. Natl. Acad. Sci. U.S.A., 96, pp. 13496-13500; Zender, L., Hutker, S., Liedtke, C., Tillmann, H.L., Zender, S., Mundt, B., Waltemathe, M., Kubicka, S., Caspase 8 small interfering RNA prevents acute liver failure in mice (2003) Proc. Natl. Acad. Sci. U.S.A., 100, pp. 7797-7802; Zhang, H., Cook, J., Nickel, J., Yu, R., Stecker, K., Myers, K., Dean, N.M., Reduction of liver Fas expression by an antisense oligonucleotide protects mice from fulminant hepatitis (2000) Nat. Biotechnol., 18, pp. 862-867; Zhang, H., Taylor, J., Luther, D., Johnston, J., Murray, S., Wyatt, J.R., Watt, A.T., Dean, N.M., Antisense oligonucleotide inhibition of Bcl-xL and Bid expression in liver regulates responses in a mouse model of Fas-induced fulminant hepatitis (2003) J. Pharmacol. Exp. Ther., 31, p. 31; Zhu, S., Stavrovskaya, I.G., Drozda, M., Kim, B.Y., Ona, V., Li, M., Sarang, S., Friedlander, R.M., Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice (2002) Nature, 417, pp. 74-78",
year = "2005",
doi = "10.1038/sj.bjp.0706079",
language = "English",
volume = "144",
pages = "275--282",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Effects of minocycline on Fas-mediated fulminant hepatitis in mice

AU - Chu, Heng-Cheng

AU - Lin, Yi-Ling

AU - Sytwu, Huey-Kang

AU - Lin, Shin-Hua

AU - Liao, Ching-Len

AU - Chao, You-Chen

N1 - 被引用次數:18 Export Date: 22 March 2016 CODEN: BJPCB 通訊地址: Liao, C.-L.161, Sec. 6, Min-Chuan E Road, Neihu, Taipei 114, Taiwan; 電子郵件: chinglen@ms1.hinet.net 化學物質/CAS: caspase 3, 169592-56-7; caspase 9, 180189-96-2; cytochrome c, 9007-43-6, 9064-84-0; liver extract, 72980-85-9; minocycline, 10118-90-8, 11006-27-2, 13614-98-7; protein Bid, 260235-79-8; Antibodies, Monoclonal; Antigens, CD95; Fas protein, mouse; Minocycline, 10118-90-8; Receptors, Tumor Necrosis Factor; anti-Fas monoclonal antibody 參考文獻: Amin, A.R., Attur, M.G., Thakker, G.D., Patel, P.D., Vyas, P.R., Patel, R.N., Patel, I.R., Abramson, S.B., A novel mechanism of action of tetracyclines: Effects on nitric oxide synthases (1996) Proc. Natl. Acad. Sci. U.S.A., 93, pp. 14014-14019; Ashkenazi, A., Dixit, V.M., Death receptors: Signaling and modulation (1998) Science, 281, pp. 1305-1308; Atillasoy, E., Berk, P.D., Fulminant hepatic failure: Pathophysiology, treatment, and survival (1995) Annu. Rev. Med., 46, pp. 181-191; Bajt, M.L., Lawson, J.A., Vonderfecht, S.L., Gujral, J.S., Jaeschke, H., Protection against Fas receptor-mediated apoptosis in hepatocytes and nonparenchymal cells by a caspase-8 inhibitor in vivo: Evidence for a postmitochondrial processing of caspase-8 (2000) Toxicol. Sci., 58, pp. 109-117; Bocker, R., Estler, C.J., Ludewig-Sandig, D., Evaluation of the hepatotoxic potential of minocycline (1991) Antimicrob. Agents Chemother., 35, pp. 1434-1436; Chang, B., Nishikawa, M., Sato, E., Inoue, M., Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis (2003) Arch. Biochem. Biophys., 411, pp. 63-72; Chen, M., Ona, V.O., Li, M., Ferrante, R.J., Fink, K.B., Zhu, S., Bian, J., Friedlander, R.M., Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease (2000) Nat. Med., 6, pp. 797-801; Du, Y., Ma, Z., Lin, S., Dodel, R.C., Gao, F., Bales, K.R., Triarhou, L.C., Paul, S.M., Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease (2001) Proc. Natl. Acad. Sci. U.S.A., 98, pp. 14669-14674; Feldmann, G., Haouzi, D., Moreau, A., Durand-Schneider, A.M., Bringuier, A., Berson, A., Mansouri, A., Pessayre, D., Opening of the mitochondrial permeability transition pore causes matrix expansion and outer membrane rupture in Fas-mediated hepatic apoptosis in mice (2000) Hepatology, 31, pp. 674-683; Galle, P.R., Hofmann, W.J., Walczak, H., Schaller, H., Otto, G., Stremmel, W., Krammer, P.H., Runkel, L., Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage (1995) J. Exp. Med., 182, pp. 1223-1230; Golub, L.M., Goodson, J.M., Lee, H.M., Vidal, A.M., McNamara, T.F., Ramamurthy, N.S., Tetracyclines inhibit tissue collagenases. Effects of ingested low-dose and local delivery systems (1985) J. Periodontol., 56, pp. 93-97; Gough, A., Chapman, S., Wagstaff, K., Emery, P., Elias, E., Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome (1996) BMJ, 312, pp. 169-172; Green, D.R., Reed, J.C., Mitochondria and apoptosis (1998) Science, 281, pp. 1309-1312; Klein, N.C., Cunha, B.A., Tetracyclines (1995) Med. Clin. N. Am., 79, pp. 789-801; Lacronique, V., Mignon, A., Fabre, M., Viollet, B., Rouquet, N., Molina, T., Porteu, A., Kahn, A., Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice (1996) Nat. Med., 2, pp. 80-86; Lawrenson, R.A., Seaman, H.E., Sundstrom, A., Williams, T.J., Farmer, R.D., Liver damage associated with minocycline use in acne: A systematic review of the published literature and pharmacovigilance data (2000) Drug Saf., 23, pp. 333-349; Li, H., Zhu, H., Xu, C.J., Yuan, J., Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis (1998) Cell, 94, pp. 491-501; Lin, S., Wei, X., Xu, Y., Yan, C., Dodel, R., Zhang, Y., Liu, J., Du, Y., Minocycline blocks 6-hydroxydopamine-induced neurotoxicity and free radical production in rat cerebellar granule neurons (2003) Life Sci., 72, pp. 1635-1641; Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., Wang, X., Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade (1997) Cell, 91, pp. 479-489; Luo, X., Budihardjo, I., Zou, H., Slaughter, C., Wang, X., Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors (1998) Cell, 94, pp. 481-490; Malassagne, B., Ferret, P.J., Hammoud, R., Tulliez, M., Bedda, S., Trebeden, H., Jaffray, P., Batteux, F., The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse (2001) Gastroenterology, 121, pp. 1451-1459; Malcolm, A., Heap, T.R., Eckstein, R.P., Lunzer, M.R., Minocycline-induced liver injury (1996) Am. J. Gastroenterol., 91, pp. 1641-1643; Miyachi, Y., Yoshioka, A., Imamura, S., Niwa, Y., Effect of antibiotics on the generation of reactive oxygen species (1986) J. Invest. Dermatol., 86, pp. 449-453; Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Nagata, S., Lethal effect of the anti-Fas antibody in mice (1993) Nature, 364, pp. 806-809; Okamoto, T., The protective effect of glycyrrhizin on anti-Fas antibody-induced hepatitis in mice (2000) Eur. J. Pharmacol., 387, pp. 229-232; Okamoto, T., Hitomi, Y., Hara, A., The protective effect of cyclosporine A on anti-Fas antibody-induced hepatitis in mice (1999) Jpn. J. Pharmacol., 79, pp. 485-488; Okamoto, T., Kawasaki, T., Hino, O., Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway (2003) Biochem. Pharmacol., 65, pp. 677-681; Okamoto, T., Okabe, S., Inhibition of anti-Fas antibody-induced hepatitis by aminoguanidine in mice (2000) Eur. J. Pharmacol., 403, pp. 277-280; Peter, M.E., Krammer, P.H., Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis (1998) Curr. Opin. Immunol., 10, pp. 545-551; Rodriguez, I., Matsuura, K., Khatib, K., Reed, J.C., Nagata, S., Vassalli, P., A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection (1996) J. Exp. Med., 183, pp. 1031-1036; Rodriguez, I., Matsuura, K., Ody, C., Nagata, S., Vassalli, P., Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death (1996) J. Exp. Med., 184, pp. 2067-2072; Sadowski, T., Steinmeyer, J., Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes (2001) J. Rheumatol., 28, pp. 336-340; Sanchez Mejia, R.O., Ona, V.O., Li, M., Friedlander, R.M., Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction (2001) Neurosurgery, 48, pp. 1393-1399. , discussion 1399-1401; Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K.J., Debatin, K.M., Peter, M.E., Two CD95 (APO-1/Fas) signaling pathways (1998) EMBO J., 17, pp. 1675-1687; Scaffidi, C., Schmitz, I., Zha, J., Korsmeyer, S.J., Krammer, P.H., Peter, M.E., Differential modulation of apoptosis sensitivity in CD95 type I and type II cells (1999) J. Biol. Chem., 274, pp. 22532-22538; Seino, K., Setoguchi, Y., Ogino, T., Kayagaki, N., Akiba, H., Nakano, H., Taniguchi, H., Fukao, K., Protection against Fas-mediated and tumor necrosis factor receptor 1-mediated liver injury by blockade of FADD without loss of nuclear factor-kappaB activation (2001) Ann. Surg., 234, pp. 681-688; Song, E., Lee, S.K., Wang, J., Ince, N., Ouyang, N., Min, J., Chen, J., Lieberman, J., RNA interference targeting Fas protects mice from fulminant hepatitis (2003) Nat. Med., 9, pp. 347-351; Strand, S., Hofmann, W.J., Grambihler, A., Hug, H., Volkmann, M., Otto, G., Wesch, H., Galle, P.R., Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis (1998) Nat. Med., 4, pp. 588-593; Tilley, B.C., Alarcon, G.S., Heyse, S.P., Trentham, D.E., Neuner, R., Kaplan, D.A., Clegg, D.O., Fowler, S.E., Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial (1995) Ann. Intern. Med., 122, pp. 81-89. , MIRA Trial Group; Woo, M., Hakem, A., Elia, A.J., Hakem, R., Duncan, G.S., Patterson, B.J., Mak, T.W., In vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes (1999) J. Immunol., 163, pp. 4909-4916; Yamamoto, M., Miura, N., Ohtake, N., Amagaya, S., Ishige, A., Sasaki, H., Komatsu, Y., Terasawa, K., Genipin, a metabolite derived from the herbal medicine Inchin-ko-to, and suppression of Fas-induced lethal liver apoptosis in mice (2000) Gastroenterology, 118, pp. 380-389; Yin, X.M., Wang, K., Gross, A., Zhao, Y., Zinkel, S., Klocke, B., Roth, K.A., Korsmeyer, S.J., Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis (1999) Nature, 400, pp. 886-891; Yrjanheikki, J., Keinanen, R., Pellikka, M., Hokfelt, T., Koistinaho, J., Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia (1998) Proc. Natl. Acad. Sci. U.S.A., 95, pp. 15769-15774; Yrjanheikki, J., Tikka, T., Keinanen, R., Goldsteins, G., Chan, P.H., Koistinaho, J., A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window (1999) Proc. Natl. Acad. Sci. U.S.A., 96, pp. 13496-13500; Zender, L., Hutker, S., Liedtke, C., Tillmann, H.L., Zender, S., Mundt, B., Waltemathe, M., Kubicka, S., Caspase 8 small interfering RNA prevents acute liver failure in mice (2003) Proc. Natl. Acad. Sci. U.S.A., 100, pp. 7797-7802; Zhang, H., Cook, J., Nickel, J., Yu, R., Stecker, K., Myers, K., Dean, N.M., Reduction of liver Fas expression by an antisense oligonucleotide protects mice from fulminant hepatitis (2000) Nat. Biotechnol., 18, pp. 862-867; Zhang, H., Taylor, J., Luther, D., Johnston, J., Murray, S., Wyatt, J.R., Watt, A.T., Dean, N.M., Antisense oligonucleotide inhibition of Bcl-xL and Bid expression in liver regulates responses in a mouse model of Fas-induced fulminant hepatitis (2003) J. Pharmacol. Exp. Ther., 31, p. 31; Zhu, S., Stavrovskaya, I.G., Drozda, M., Kim, B.Y., Ona, V., Li, M., Sarang, S., Friedlander, R.M., Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice (2002) Nature, 417, pp. 74-78

PY - 2005

Y1 - 2005

N2 - Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. Intraperitoneal injection of Jo2 (0.6 μg g -1) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg -1) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.

AB - Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. Intraperitoneal injection of Jo2 (0.6 μg g -1) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg -1) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.

KW - Caspase

KW - Cytochrome c

KW - Fas

KW - Fulminant hepatitis

KW - Minocycline

KW - Mitochondria

KW - caspase 3

KW - caspase 9

KW - cytochrome c

KW - Fas antibody

KW - Fas antigen

KW - jo2 antibody

KW - liver extract

KW - minocycline

KW - protein Bid

KW - unclassified drug

KW - alanine aminotransferase blood level

KW - animal experiment

KW - animal model

KW - animal tissue

KW - antiinflammatory activity

KW - apoptosis

KW - article

KW - aspartate aminotransferase blood level

KW - controlled study

KW - disease model

KW - drug effect

KW - enzyme activation

KW - enzyme release

KW - hepatitis

KW - histopathology

KW - kinetics

KW - liver mitochondrion

KW - male

KW - mouse

KW - mouse strain

KW - nonhuman

KW - priority journal

KW - survival

KW - Animals

KW - Antibodies, Monoclonal

KW - Antigens, CD95

KW - Dose-Response Relationship, Drug

KW - Liver

KW - Liver Failure, Acute

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Receptors, Tumor Necrosis Factor

U2 - 10.1038/sj.bjp.0706079

DO - 10.1038/sj.bjp.0706079

M3 - Article

VL - 144

SP - 275

EP - 282

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -