論文 - 詳細
RRC ID | 6186 |
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著者 | Gurzov EN, Ortis F, Bakiri L, Wagner EF, Eizirik DL. |
タイトル | JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells. |
ジャーナル | 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. |
巻・号 | 3(8) |
ページ | e3030 |
公開日 | 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 | 2.74 |
引用数 | 45 |
WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
リソース情報 | |
遺伝子材料 | AxCArJunB (forward) (RDB02774) |