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Heat Shock Protein 90 Inhibitor Induces Apoptosis and Attenuates Activation of Hepatic Stellate Cells
DC Field | Value | Language |
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dc.contributor.author | Myung, Sun Jung | - |
dc.contributor.author | Yoon, Jung-Hwan | - |
dc.contributor.author | Kim, Bo Hyun | - |
dc.contributor.author | Lee, Jeong-Hoon | - |
dc.contributor.author | Lee, Hyo-Suk | - |
dc.contributor.author | Jung, Eun Uk | - |
dc.date.accessioned | 2012-06-26T05:27:27Z | - |
dc.date.available | 2012-06-26T05:27:27Z | - |
dc.date.issued | 2009-07 | - |
dc.identifier.citation | JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS; Vol.330 1; 276-282 | ko_KR |
dc.identifier.issn | 0022-3565 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77431 | - |
dc.description.abstract | Activated hepatic stellate cells (HSCs) are major participants in hepatic fibrosis; thus, the induction of HSC apoptosis has been proposed as an antifibrotic treatment strategy. Heat shock protein (Hsp) 90 is a molecular chaperone that stabilizes major signal transduction proteins, and its inhibitors have antitumor activity. In this study, the susceptibility of HSCs to an Hsp90 inhibitor was evaluated. LX-2 cells, an immortalized human HSC line, 17-(allylamino)-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, and monensin, an acidic sphingomyelinase inhibitor, were used in this study. Cellular apoptosis was quantified by 4`,6-diamidino-2-phenylindole dihydrochloride staining, and signaling cascades were explored using immunoblotting and immunoprecipitation techniques. Nuclear factor (NF) kappa B activities were evaluated by immunofluorescent microscopy and enzyme-linked immunosorbent assay. Collagen alpha 1 and alpha-smooth muscle actin expressions were determined by real-time reverse transcription-polymerase chain reaction and immunoblotting, respectively. It was found that 17AAG induced HSC apoptosis and that caspase 8 cleavage preceded the downstream activation of apoptotic signaling cascades. Furthermore, this caspase 8 activation was dependent on ceramide generation by acidic sphingomyelinase. In addition, 17AAG prevented NF kappa B nuclear translocation and activation, specifically by inducing complex formation between NF kappa B and the glucocorticoid receptor. In accordance, NF kappa B-dependent cellular FLICE-like inhibitory protein expression level was found to be reduced by 17AAG. Finally, 17AAG down-regulated collagen alpha 1 and alpha-smooth muscle actin expression levels in HSCs before inducing apoptosis. These results demonstrate that the Hsp90 inhibitor induces HSC apoptosis via a sphingomyelinase- and NF kappa B-dependent mechanism. Because this inhibitor also reduces HSC activation before apoptosis, Hsp90 inhibitor treatment might be therapeutically useful as an antifibrotic strategy in a variety of liver diseases. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | ko_KR |
dc.title | Heat Shock Protein 90 Inhibitor Induces Apoptosis and Attenuates Activation of Hepatic Stellate Cells | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 명선정 | - |
dc.contributor.AlternativeAuthor | 윤정환 | - |
dc.contributor.AlternativeAuthor | 김보현 | - |
dc.contributor.AlternativeAuthor | 이정훈 | - |
dc.contributor.AlternativeAuthor | 정은욱 | - |
dc.contributor.AlternativeAuthor | 이효석 | - |
dc.identifier.doi | 10.1124/jpet.109.151860 | - |
dc.citation.journaltitle | JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | - |
dc.description.citedreference | Tokunaga T, 2008, DIGEST DIS SCI, V53, P2989, DOI 10.1007/s10620-008-0241-y | - |
dc.description.citedreference | DeLeve LD, 2008, HEPATOLOGY, V48, P920, DOI 10.1002/hep.22351 | - |
dc.description.citedreference | Hannivoort RA, 2008, HEPATOLOGY, V48, P624, DOI 10.1002/hep.22346 | - |
dc.description.citedreference | Lanneau D, 2008, J CELL MOL MED, V12, P743, DOI 10.1111/j.1582-4934.2008.00273.x | - |
dc.description.citedreference | Langer DA, 2008, HEPATOLOGY, V47, P1983, DOI 10.1002/hep.22285 | - |
dc.description.citedreference | Al Shaer L, 2008, BRIT J HAEMATOL, V141, P483, DOI 10.1111/j.1365-2141.2008.07053.x | - |
dc.description.citedreference | Watson MR, 2008, J HEPATOL, V48, P589, DOI 10.1016/j.jhep.2007.12.019 | - |
dc.description.citedreference | HOLMES JL, 2008, CANCER RES, V68, P1188 | - |
dc.description.citedreference | Meyer PN, 2008, LEUKEMIA RES, V32, P143, DOI 10.1016/j.leukres.2007.05.009 | - |
dc.description.citedreference | Jeon YK, 2007, J PATHOL, V213, P170, DOI 10.1002/path.2219 | - |
dc.description.citedreference | Nieto N, 2007, HEPATOLOGY, V45, P1433, DOI 10.1002/hep.21659 | - |
dc.description.citedreference | Novo E, 2006, GUT, V55, P1174, DOI 10.1136/gut.2005.082701 | - |
dc.description.citedreference | Kawada N, 2006, GUT, V55, P1073, DOI 10.1136/gut.2005.090449 | - |
dc.description.citedreference | Cullman SB, 2006, SEMIN ONCOL, V33, P457, DOI 10.1053/j.seminoncol.2006.04.001 | - |
dc.description.citedreference | Desmet VJ, 2005, DIGEST LIVER DIS, V37, P909, DOI 10.1016/j.dld.2005.08.007 | - |
dc.description.citedreference | Elsharkawy AM, 2005, APOPTOSIS, V10, P927, DOI 10.1007/s10495-005-1055-4 | - |
dc.description.citedreference | Carpino G, 2005, DIGEST LIVER DIS, V37, P349, DOI 10.1016/j.dld.2004.11.009 | - |
dc.description.citedreference | Wells RG, 2005, J CLIN GASTROENTEROL, V39, pS158 | - |
dc.description.citedreference | Viatour P, 2005, TRENDS BIOCHEM SCI, V30, P43, DOI 10.1016/j.tiba.2004.11.009 | - |
dc.description.citedreference | Oakley F, 2005, GASTROENTEROLOGY, V128, P108, DOI 10.1053/j.gastro.2004.10.003 | - |
dc.description.citedreference | Lin CF, 2004, J BIOL CHEM, V279, P40755, DOI 10.1074/jbc.M404726200 | - |
dc.description.citedreference | Desmet VJ, 2004, J HEPATOL, V40, P860, DOI 10.1016/j.jhep.2004.03.007 | - |
dc.description.citedreference | Buttner C, 2004, J CELL PHYSIOL, V198, P248, DOI 10.1002/jcp.10395 | - |
dc.description.citedreference | Tago K, 2004, MOL CELL ENDOCRINOL, V213, P131, DOI 10.1016/j.ce.2003.10.057 | - |
dc.description.citedreference | Yang J, 2004, CELL BIOCHEM BIOPHYS, V40, P323 | - |
dc.description.citedreference | Kolesnick R, 2003, ONCOGENE, V22, P5897, DOI 10.1038/sj.onc.1206702 | - |
dc.description.citedreference | Goetz MP, 2003, ANN ONCOL, V14, P1169, DOI 10.1093/annonc/mdg316 | - |
dc.description.citedreference | Sato M, 2003, CELL STRUCT FUNCT, V28, P105 | - |
dc.description.citedreference | NECKERS L, 2003, CURR OPIN ONCOL, V15, P419 | - |
dc.description.citedreference | HUI AY, 2003, EXPERT REV MOL MED, V5, P1 | - |
dc.description.citedreference | Taimr P, 2003, HEPATOLOGY, V37, P87, DOI 10.1053/jhep.2003.50002 | - |
dc.description.citedreference | Panaretou B, 2002, MOL CELL, V10, P1307 | - |
dc.description.citedreference | Mann DA, 2002, GUT, V50, P891 | - |
dc.description.citedreference | Chen GQ, 2002, MOL CELL, V9, P401 | - |
dc.description.citedreference | Iredale JP, 2001, SEMIN LIVER DIS, V21, P427 | - |
dc.description.citedreference | Pinzani M, 2001, SEMIN LIVER DIS, V21, P397 | - |
dc.description.citedreference | Kreuz S, 2001, MOL CELL BIOL, V21, P3964 | - |
dc.description.citedreference | Friedman SL, 2000, J BIOL CHEM, V275, P2247 | - |
dc.description.citedreference | Arthur MJP, 1999, ALCOHOL CLIN EXP RES, V23, P940 | - |
dc.description.citedreference | OBEID LM, 1995, J CELL BIOCHEM, V58, P191 | - |
dc.description.tc | 4 | - |
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