RRC ID 6186
Author Gurzov EN, Ortis F, Bakiri L, Wagner EF, Eizirik DL.
Title JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.
Journal PLoS One
Abstract 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.
Volume 3(8)
Pages e3030
Published 2008-8-21
DOI 10.1371/journal.pone.0003030
PMID 18716665
PMC PMC2516602
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
IF 2.776
Times Cited 45
DNA material AxCArJunB (forward) (RDB02774)