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: Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of Bid cleavage. | García et al. Arthritis Research Therapy 2010 12 R33 http content 12 1 R33 RESEARCH ARTICLE Open Access Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of Bid cleavage Samuel García 1 Myriam Liz1 Juan J Gomez-Reino1 2 and Carmen Conde 1 Abstract Introduction Synovial hyperplasia is a main feature of rheumatoid arthritis pathology that leads to cartilage and bone damage in the inflamed joints. Impaired apoptosis of resident synoviocytes is pivotal in this process. Apoptosis resistance seems to involve defects in the extrinsic and intrinsic apoptotic pathways. The aim of this study was to investigate the association of PI3Kinase Akt and the mitochondrial apoptotic pathway in the resistance of rheumatoid arthritis RA fibroblast like synovial cells FLS to Fas-mediated apoptosis. Methods Apoptosis was assessed by ELISA quantification of nucleosomal release Hoechst staining and activated caspase-3 7 measure in cultured RA FLS stimulated with anti-Fas antibody. Two Phosphoinositol-3-kinase protein Kinase B PI3 Kinase inhibitors Wortmannine and LY294002 were used before anti-Fas stimulation. Proapoptotic BH3 interacting domain death agonist Bid was suppressed in RA FLS by small interfering RNA siRNA transfection. Bid was overexpressed by transfection with the pDsRed2-Bid vector. Phosphorylated Akt caspase-9 and Bid expression were analysed by western blot. Results PI3 kinase inhibition sensitizes RA FLS to Fas-induced apoptosis by increasing cleavage of Bid protein. Bid suppression completely abrogated Fas-induced apoptosis and Bid overexpression highly increased apoptotic rate of RA FLS in association with cleavage of caspase-9. Conclusions In RA FLS phosphorylation of Akt protects against Fas-induced apoptosis through inhibition of Bid cleavage. The connection between the extrinsic and the intrinsic apoptotic pathways are critical in this Fas- mediated apoptosis and points to PI3Kinase as potential .
