Limited GADD45α expression and function in IL-1β toxicity towards insulin-producing cells.

Lukasz Skalniak; Ewa Gurgul-Convey; Katarzyna Okreglicka; Anna Skalniak; Jolanta Jura

doi:10.18388/abp.2013_2026

Lukasz Skalniak Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.;
Ewa Gurgul-Convey Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.;
Katarzyna Okreglicka Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.;
Anna Skalniak Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.;
Jolanta Jura Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.;

DOI: https://doi.org/10.18388/abp.2013_2026

Abstract

Growth arrest and DNA damage-inducible (GADD) 45 proteins are regulators of cell death and survival. The proinflammatory cytokine IL-1β strongly increases the level of the transcript encoding GADD45α in rat insulin-producing INS-1E cells. The activation of Gadd45α gene is clearly dependent on JNK and NF-κB activation and the synthesis of the secondary mediator nitric oxide (NO). Interestingly, the observed twelve-fold increase in the GADD45α-coding transcript level is not followed by increased expression of GADD45α at the protein level. An analysis of IL-1β toxicity in INS-1E cells overexpressing GADD45α revealed no correlation between the GADD45α protein level and the sensitivity to IL-1β toxicity. These findings suggest that the potential engagement of GADD45α in IL-1β toxicity towards beta cells is limited to the effects induced by the basal expression level of this protein.