Limited GADD45 alpha expression and function in IL-1 beta toxicity towards insulin-producing cells

作者：Skalniak Lukasz; Gurgul Convey Ewa; Okreglicka Katarzyna; Skalniak Anna; Jura Jolanta^*

来源：Acta Biochimica Polonica, 2013, 60(4): 595-602.

• GADD45
• IL-1 beta
• insulin-producing cells
• type 1 diabetes

Growth arrest and DNA damage-inducible (GADD) 45 proteins are regulators of cell death and survival. The proinflammatory cytokine IL-1 beta strongly increases the level of the transcript encoding GADD45 alpha in rat insulin-producing INS-1E cells. The activation of GADD45 alpha gene is clearly dependent on JNK and NF-kappa B activation and the synthesis of the secondary mediator nitric oxide (NO). Interestingly, the observed twelve-fold increase in the GADD45 alpha-coding transcript level is not followed by increased expression of GADD45 alpha at the protein level. An analysis of IL-1 beta toxicity in INS-1E cells overexpressing GADD45 alpha revealed no correlation between the GADD45 alpha protein level and the sensitivity to IL-1 beta toxicity. These findings suggest that the potential engagement of GADD45 alpha in IL-1 beta toxicity towards beta cells is limited to the effects induced by the basal expression level of this protein.

• 出版日期2013