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| 1 | Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells显示文摘AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma. | Yucel Ustundag Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，6： | 9 |
| 2 | THE GREATER VULNERABILITY OF BILE DUCT CELLS TO REOXYGENATION INJURY THAN TO ANOXIA显示文摘 | KEITH NOACK STEVEN F. BRONK AKINOBU KATO GREGORY J. GORES | 1993 | Transplantation1993，，3： | 3 |
| 3 | Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse显示文摘AIM:To ascertain whether constitutive androstane receptor(CAR)activation by 1,4-bis-2-(3,5,-dichloropyridyloxy)benzene(TCPOBOP)modulates steatohepatitis in the methionine choline-deficient(MCD)diet-fed animal.METHODS:C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist,TCPOBOP,or the CAR inverse agonist,androstanol.RESULTS:Expression of CYP2B10 and CYP3A11,known CAR target genes,increased 30-fold and 45-fold,respectively,in TCPOBOP-treated mice fed the MCD diet.TCPOBOP treatment reduced hepatic steatosis(44.6 ± 5.4% vs 30.4 ± 4.5%,P < 0.05)and serum triglyceride levels(48 ± 8 vs 20 ± 1 mg/dL,P < 0.05)in MCD diet-fed mice as compared with the standard diet-fed mice.This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal ω-oxidation and peroxisomal β-oxidation,namely CYP4A10,LPBE,and 3-ketoacyl-CoA thiolase.The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation.In contrast,androstanol was without effect on any of the above parameters.CONCLUSION:CAR activation stimulates induction of genes involved in fatty acid oxidation,and ameliorates hepatic steatosis,apoptosis and inflammation. | Edwina S Baskin-Bey Akira Anan Hajime Isomoto Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，42： | 3 |
| 4 | A hedgehog survival pathway in ‘undead’ lipotoxic hepatocytes显示文摘 | Keisuke Kakisaka Sophie C. Cazanave Nathan W. Werneburg Nataliya Razumilava Joachim C. Mertens Steve F. Bronk Gregory J. Gores | 2012 | Journal of Hepatology2012，，4： | 2 |
| 5 | cFL IPL prevents TRA L-induced apoptosis of hepatocellular carcinoma cells by inhibiting the lysosomal pathway of apoptosis显示文摘 | Guicciardi M E Bronk S F Wemeburg M W | 2007 | Am J Physiol Gastrointest Liver Physiol2007，292，5： | 1 |
| 6 | Effect of acute normobaric hypoxia on quadriceps integrated EMG and blood metabolites during incremental exercise to exhaustion显示文摘 | Taylor A D Bronks R | 1996 | Eur J Appl Physiol1996，73，12： | 1 |
| 7 | Viral fusogenic membrane glycoprotein expression causes syncytia formation with bioenergetic cell death:implications for gene therapy显示文摘 | HIGUCHI H BRONK S F BATEMAN A | 2000 | Cancer Res2000，60，： | 1 |
| 8 | cFLIPL prevents TRAIL-induced apoptosis of hepatocellular carcinoma cells by inhibiting the lysosomal pathway of apoptosis显示文摘 | Guicciardi ME Bronk SF Werneburg NW | 2007 | Am J Physiol Gastrointest Liver Physiol2007，292，5： | 1 |
| 9 | Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induced lysosomal translocation of proapoptotic effectors is mediated by phosphofurin acidic cluster sorting protein-2 ( PACS- 2) 显示文摘 | Werneburg NW Bronk SF Guicciardi ME | 2012 | J Biol Chem2012，287，24： | 1 |
| 10 | Dissolved organic nitrogen:a dynamic participant in aquatic ecosystems显示文摘 | Berman T Bronk D A | 2003 | Aquatic Microbial Ecology2003，31，3： | 1 |
| 11 | Free fatty acids promote hepati clipotoxieity by stimulating TNF alpha expression via a lysose real pathway显示文摘 | Feldstein A E Werneburg N W Canbay A Guicciardi M E Bronk S F Rydzewski R | 2004 | Hepatology2004，40，： | 1 |
| 12 | mir-29 regulates Mcl-1 protein expression and apoptosis 显示文摘 | Mott JL Kobayashi S Bronk SF | 2007 | Oncogene2007，26，42： | 1 |
| 13 | Activated of hepatic stellate cells in vitro is associated with increased intracellular levels of praoxidants显示文摘 | Bronk E Oneil R Higashikubo R | 1999 | Hepatogy1999，30，42： | 1 |
| 14 | Training-specific muscle architecture adaptation after 5-wk training in athletes显示文摘 | Blazevich A J Gill N D Bronks R | 2003 | Med Sci Sports Exerc2003，35，12： | 1 |
| 15 | Identification of Bmi-1-interacting proteins as constituents of a multimeric mammalian polycomb complex 显示文摘 | Alkema M J Bronk M Verhoeven E | 1997 | Genes Dev1997，11，2： | 1 |
| 16 | DON as a source of bioavailable nitrogen for phytoplankton 显示文摘 | BRONK D A SEE J H BRADLEY P | 2007 | Biogeosciences2007，4，： | 1 |
| 17 | Inorganic and organic nitrogen cycling in Chesapeake Bay:autotrophic versus heterotrophic process and relationships to carbon flux显示文摘 | Bronk D A Glibert P M Malone T C | 1998 | Aquatic Microbial Ecology1998，15，： | 1 |
| 18 | Dissolved organic nitrogen: A dynamic participant in aquatic ecosystems 显示文摘 | Berman T Bronk D A | 2003 | Aquatic Microbial Ecology2003，31，3： | 1 |
| 19 | Photochemical release of biologically available nitrogen from aquatic dissolved organic matter显示文摘 | Bushaw K L Zepp R G Ta-r M A Schulz-Jander D Bourbonniere R A Hodson R E Miller W L Bronk D A Moran M A | 2002 | Nature2002，381，： | 1 |
| 20 | Total dissolved nitrogen anglysis:Comparisons between persulfate,UV,and high temperature oxidation methods显示文摘 | Bronk D A Lomas M W Glibert P M | 2000 | Marine Chemistry2000，69，： | 1 |
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