title: Limited GADD45α expression and function in IL-1β toxicity towards insulin-producing cells.
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.
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Skalniak
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gurgul-Convey
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Okreglicka
authors.affiliation: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Skalniak
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jura
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D007328:Insulin; D053583:Interleukin-1beta; D009569:Nitric Oxide; D009687:Nuclear Proteins; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins