Unknown

Dataset Information

0

JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.


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.

SUBMITTER: Gurzov EN 

PROVIDER: S-EPMC2516602 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

altmetric image

Publications

JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.

Gurzov Esteban N EN   Ortis Fernanda F   Bakiri Latifa L   Wagner Erwin F EF   Eizirik Decio L DL  

PloS one 20080821 8


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 i  ...[more]

Similar Datasets

| S-EPMC3781485 | biostudies-literature
| S-EPMC7762434 | biostudies-literature
| S-EPMC3071830 | biostudies-literature
| S-EPMC8137563 | biostudies-literature
| S-EPMC3675788 | biostudies-literature
| S-EPMC4084580 | biostudies-literature
| S-EPMC7112150 | biostudies-literature
| S-EPMC8285784 | biostudies-literature
| S-EPMC8990750 | biostudies-literature
| S-EPMC8800039 | biostudies-literature