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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 | Design and Implementation of a Personal Computer Authorization System using Color Detection 显示文摘 | F Yucel O Oral N Caglayan | 2011 | Electronics and Electrical Engineering2011，115，9： | 1 |
| 3 | Anatomical variations of medial umbilical ligament: clinical significance in laparoscopic exploration of children 显示文摘 | Tokar B Yucel F | 2009 | Pediatr Surg Int2009，25，12： | 1 |
| 4 | Erythrocyte membrane glycation and Na( + ) - K ( -) levels in NIDDM 显示文摘 | Umudum F Yucel 0 Sahin Y | 2002 | J Diabetes Complications2002，16，5： | 1 |
| 5 | Antioxidant responses of shoots and roots of lentil to NaCl-salinity stress显示文摘 | Bangeoglu E Eyidogan F Yucel M | | 0，，： | 1 |
| 6 | The efficacy of intrathecal morphine in post-thoracotomy pain management显示文摘 | ASKAR F Z KOCABAS S YUCEL S | | 0，，03： | 1 |
| 7 | Development of mouse hybridomas by fusion of myeloma cells with lymphocytes derived from spleen, lymph node, and bone marrow 显示文摘 | Basalp A Yucel F | 2003 | Hybrid Hvbridomics2003，22，5： | 1 |
| 8 | Penetrating aorticulcers: diagnosis with MR in aging显示文摘 | Yucel E K Steinberg F L Egglin T K | 1990 | Radiology1990，177，： | 1 |
| 9 | Antioxidant responses of shoots and roots of lentil to NaCl-salinity stress显示文摘 | Bandeoglu E Eyidogan F Yucel M | 2004 | Plant Growth Regul2004，42，： | 1 |
| 10 | Anatomical variations of medial umbilical ligament: clinical significance in laparoseopie exploration of children 显示文摘 | Tokar B Yucel F | 2009 | Pediatr surg Int2009，25，： | 1 |
| 11 | Chloride removal from zinc ash显示文摘 | Cinar Sahin F Derin B Yucel O | 2000 | Scandinavian Journal of Metallurgy2000，29，5： | 1 |
| 12 | Primary omental pregnancy presenting with hemorrhagic shock: A case re- port 显示文摘 | Ozdemir I Demirci F Yucel O | 2003 | Gynecol Obstet Invest2003，55，2： | 1 |
| 13 | Plasma homocysteine levels in noninsulin-dependent diabetes mellitus with retinopathy and neo- vascular glaucoma显示文摘 | Yueel I Yucel G Muftuoglu F | 2004 | Int Ophthalmol2004，25，4： | 1 |
| 14 | An Integrated fuzzy-lp approach for a supplier selection problem in supply chain man- agement显示文摘 | Guneri A F Yucel A Ayyildiz G | 2009 | Expert Systems with Applications2009，36，5： | 1 |
| 15 | Primary omental pregnancy presenting with hemorrhagic shock显示文摘 | Ozdemir I Demirei F Yucel O | 2003 | Gynecol Obstet Invest2003，55，2： | 1 |
| 16 | The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol 显示文摘 | Inan UU Ermis SS Orman A Onrat E Yucel A Ozturk F | 2004 | J Ocul Pharmacol Ther2004，20，4： | 1 |
| 17 | Effect of dentin bond- ing and ferrule preparation on the fracture strength of crowned teeth restored with dowels and amalgam cores显示文摘 | Aykent F Kalkan M Yucel MT | 2006 | JProsthet Dent2006，95，4： | 1 |
| 18 | A weighted additive fuzzy programming approach for multi-criteria supplier selection显示文摘 | Yucel A GUneri A F | 2010 | Expert Sys- tems with Applications2010，38，5： | 1 |
| 19 | Antioxidant responses of shoots and roots of lentil to NaC1 - salinity stress显示文摘 | Bandeoglu E Eyidogan F Yucel M | 2004 | Journal of Plant Growth Regulation2004，42，： | 1 |
| 20 | Production and characterization of monoclonal antibodies against hepatitis B viruses anti application of a quick sandwich ELISA显示文摘 | Yucel F Manav A Basalp A | 2003 | Hybrid Hybridomics2003，22，3： | 1 |
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