tailieunhanh - Báo cáo y học: " Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress. | Shin et al. Arthritis Research Therapy 2010 12 R19 http content 12 1 R19 RESEARCH ARTICLE Open Access Autophagy induction and CHOP under-expression promotes survival of fibroblasts from rheumatoid arthritis patients under endoplasmic reticulum stress 1 2 2 2 3 4 5 Yong-Joo Shin Song-Hee Han Do-Sung Kim Geum-Hwa Lee Wan-Hee Yoo Yong-Mo Kang Je-Yong Choi VriHA li I nn6 7 Ccinii m i II I Dtỉ rlz6 7 Ceil I l-k i loonn8 I lx 1 m i-TnQ IfiirY - hiTid 2 I Ix I in- 12 lonnn10 Yong Chul Lee Seoung Ju Park Seul-Ki Jeong Hyung-Tae Kim Soo-Wan Chae Hyun-Ja Jeong Hyung-Ryong Kim11 Han-Jung Chae2 7 Abstract Introduction Synovial fibroblasts from rheumatoid arthritis show resistance to apoptotic stimuli indicating they may be difficult to treat. To clearly understand these mechanisms of resistance rheumatoid and osteoarthritis synovial fibroblasts RASF and OASF were exposed to endoplasmic reticulum ER stress such as thapsigargin Ca2 -ATPase inhibitor. Methods Fibroblasts were assessed microscopically for cell viability by trypan blue exclusion and for autophagic cells by LC-3II formation. Caspase-3 activity was measured as aminomethyl-coumarin AMC liberated from AC-DEVD-AMC. Immunoblotting was performed to compare protein expression in OASF and RASF. Results ER stress caused cell death in OASF but not in RASF. Thapsigargin a Ca2 -ATPase inhibitor did not change the expression of GRP78 an ER chaperone in OASF and RASF but induced another ER stress protein CCAAT enhancer binding protein C EBP homologous protein CHOP differently showing high levels in OASF and low levels in RASF. Thapsigargin increased the autophagy response in RASF with autophagosome formation beclin expression and LC3-II conversion. Transfection with beclin siRNA inhibited autophagy and increased the susceptibility to ER stress-induced cell death. On the other hand CHOP siRNA increased autophagy and improved cell survival especially in RASF indicating that CHOP is involved in regulation of .