Reference - Detail
|Author||Gurzov EN, Ortis F, Bakiri L, Wagner EF, Eizirik DL.|
|Title||JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.|
Cytokines contribute to pancreatic beta-cell apoptosis in type 1 diabetes (T1D) by modulation of beta-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated beta-cell dysfunction and death. The cytokines IL-1beta+IFN-gamma induced an early and transitory upregulation of JunB by NF-kappaB activation. Knockdown of JunB by RNA interference increased cytokine-mediated expression of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers, leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in purified rat primary beta-cells. JunB knockdown beta-cells and junB(-/-) fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished iNOS and ER markers expression and protected beta-cells from cytokine-induced cell death. These findings demonstrate a novel and unexpected role for JunB as a regulator of defense mechanisms against cytokine- and ER stress-mediated apoptosis.
|MeSH||3T3 Cells Adenoviridae Animals Apoptosis Cell Death Cells, Cultured Endoplasmic Reticulum / physiology* Fibroblasts / cytology Fibroblasts / physiology Gene Deletion Genetic Vectors Insulin-Secreting Cells / cytology Insulin-Secreting Cells / physiology* Mice Nitric Oxide / physiology Proto-Oncogene Proteins c-jun / deficiency Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / physiology* Rats Rats, Wistar|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|DNA material||AxCArJunB (forward) (RDB02774)|