[Effect of ubiquitin-proteasome pathway on TRAIL inducing apoptosis].
OBJECTIVE
To determine the influence of ubiquitin-proteasome in regulating the TRAIL-mediated apoptosis.


METHODS
RASF cells and SCID mice were divided into 4 groups treated with PBS,anti-DR5, lactacystin, and anti-DR5 plus lactacystin. The apoptosis of cells was detected with Hoechst 33342 and TUNEL. The effect of caspase inhibitor on cell apoptosis was analysed with Hoechst 33342 and Luminescent ATP Lite.


RESULTS
Block ubiquitin-proteasome with lactacystin, a highly specific and irreversible proteasome inhibitor, induced 95% cell apoptosis both in vitro and in vivo. In contrast, there was no apoptosis of cells after the treatment with anti-DR5 antibody or lactacystin alone.


CONCLUSIONS
The inhibition of ubiquitin-proteasome pathway can sensitize rheumatoid arthritis synovial fibroblast cells to TRAIL- induced apoptosis, and the activation of caspase 8 and caspase 4 is necessary in this process.
Yang
Xin-Wen
XW
Department of Occupational and Environmental Health, School of Public Health, Central South University, Changsha 410078, China.
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000473:pathology; D002460:Cell Line; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D046988:Proteasome Endopeptidase Complex / Q000494:pharmacology*; D011897:Random Allocation; D013583:Synovial Membrane / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D025801:Ubiquitin / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex