Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
The Sjogren's Syndrome-Related Autoantigen Ro52 Is a Pro-Apoptotic Molecule Upon Oxidative Stress.
Jauharoh1, Siti NA, Kawano1, Seiji, Saegusa1, Jun, Sugimoto1, Takeshi, Sugiyama1, Daisuke, Tokuno1, Osamu, Kurimoto1, Chiyo
Ro52/TRIM21, is an autoantigen, which has been known to play important roles in the pathogenesis of several systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren's syndrome. Recent studies revealed that Ro52 has an E3 ligase activity and may ubiquitinate cellular, as well as nuclear, proteins important for anti-viral immunity. It has been reported that IFN-a induces Ro52 translocation from the cytoplasm to the nucleus in a p53-dependent manner. We have previously reported that during stress exposure, Ro52 undergoes stimulating agent-specific intracellular translocation.
In the present study, to investigate the role of Ro52 upon stress exposure, we performed transient transfection with siRNA against Ro52 on HeLa cells. These transfectants were stimulated with H2O2, diamide, IFN-a and g-irradiation, and were then subjected to Annexin-V fluorescent staining and TUNEL assay for apoptosis detection. Furthermore, to elucidate whether the nuclear translocation of Ro52 is required in Ro52-mediated apoptosis, we analyzed the expression of Ro52 protein on the nuclear and cytoplasmic fractions by Western blot analysis.
We found that the Ro52low HeLa cells were significantly more resistant to apoptosis induced by H2O2, as well as various other types of stimuli, compared to those of the control HeLa cells. Moreover, we showed that H2O2 and IFN-a, but not diamide or g-irradiation, induced the translocation of Ro52 protein from the cytoplasm to the nucleus.
Our data suggested that Ro52 may be a pro-apoptotic molecule and the nuclear translocation of Ro52 is not necessary in Ro52-associated apoptosis.
To cite this abstract, please use the following information:
Jauharoh, Siti NA, Kawano, Seiji, Saegusa, Jun, Sugimoto, Takeshi, Sugiyama, Daisuke, Tokuno, Osamu, et al; The Sjogren's Syndrome-Related Autoantigen Ro52 Is a Pro-Apoptotic Molecule Upon Oxidative Stress. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :493