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| 1 | CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes显示文摘AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling. | Toni Urbanik Bruno Christian Koehler Laura Wolpert Christin Elbner Anna-Lena Scherr Thomas Longerich Nicole Kautz Stefan Welte Nadine Hovelmeyer Dirk Jager Ari Waisman Henning Schulze-Bergkamen | 2014 | World Journal of Gastroenterology2014,20,45: | 3 |
| 2 | Prevalence of Alzheimer Disease in US States显示文摘 | Jennifer Weuve Liesi E. Hebert Paul A. Scherr Denis A. Evans | 2015 | Epidemiology2015,,1: | 2 |
| 3 | Alzheimer disease in the United States (2010–2050) estimated using the 2010 census显示文摘 | Liesi E. Hebert Jennifer Weuve Paul A. Scherr Denis A. Evans | 2013 | Neurology2013,,19: | 2 |
| 4 | Gene silencing by small regulatory RNAs in mammalian cells显示文摘 | EDER M | 2007 | Cell Cycle2007,6,: | 1 |
| 5 | Theory and application of passive SAW radio transponders as sensors 显示文摘 | Gerd scholl Thomas Ostertag Holger Scherr Ulrich Wolff Frank Schmidt | 1998 | IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control1998,45,5: | 1 |
| 6 | Age-speci?cincidence of Alzheimer's disease in a community population显示文摘 | Hebert LE Scherr PA Beckett LA | 1995 | Jama1995,273,: | 1 |
| 7 | Prostate biopsy techniques and indications:When,where,and how显示文摘 | Scherr DS Eastham J Ohori M | 2002 | Semin Urol Oncol2002,20,1: | 1 |
| 8 | CD7 in acute myeloid leukemia:correlation with loss of wild-type CEBPA,consequence of epigenetic regulation显示文摘 | Rohrs S Scherr M Romani J | | 0,,: | 1 |
| 9 | Enhanced sensitivity to inhibition of SHP2,STAT5,and Gab2 expression in chronic myeloid leukemia (CML)显示文摘 | Scherr M Chaturvedi A Battrner K | 2006 | {H}Blood2006,,08: | 1 |
| 10 | Alzheimer disease in the United States (2010-2050) estimated using the 2010 census 显示文摘 | Hebert LE Weuve J Scherr PA | 2013 | Neurology2013,80,19: | 1 |
| 11 | Peripheral primitive neuroectodermal tumor of the vulva 显示文摘 | SCHERR G R D'Ablaing III G OUZOUNIAN J G | 1994 | Gynecol Oncol1994,54,: | 1 |
| 12 | Specific inhibition of ber - abl gene expression by small interfering RNA 显示文摘 | Scherr M Battmer K Winkler T | 2003 | Blood2003,101,4: | 1 |
| 13 | Reduction of STAT3expression induces mitochondrial dysfunction and autophagy incardiac HL-1 cells显示文摘 | Elschami M Scherr M Philippens B | 2013 | Eur J Cell Biol2013,92,1: | 1 |
| 14 | Mzheimer disease in the US population: prevalence estimates using the 2000 census 显示文摘 | Hebert LE Scherr PA Bienias JL | 2003 | Arch Neurol2003,60,: | 1 |
| 15 | Stable RNA interference (RNAi) as an option for anti-bcr-abl therapy显示文摘 | SCHERR M BATTMER K SCHULTHEIS B | 2005 | Gene Ther2005,12,1: | 1 |
| 16 | Stable RNA interference (RNAi) as an option for anti-bcr-abl therapy显示文摘 | Scherr M Battmer K Schultheis B | 2005 | Gene Ther2005,12,1: | 1 |
| 17 | Gene silencing by small regulatory RNAs in mammalian cells 显示文摘 | Scherr M Eder M | 2007 | Cell Cycle2007,6,4: | 1 |
| 18 | Association of incident alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study显示文摘 | Morris MC Scherr PA Hebert LE | 2001 | Arch Neurol2001,58,10: | 1 |
| 19 | Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint显示文摘 | Scherr D Khairy P Miyazaki S | 2014 | Circ Arrhythm Electrophysiol2014,9,2: | 1 |
| 20 | Educational at- tainment and cognitive decline in old age显示文摘 | WIISON RS HEBERT LE SCHERR PA | 2009 | Neurology2009,72,5: | 1 |