Role for Activating Transcription Factor 3 in Stress-Induced β-Cell Apoptosis
| Autor: | Tsonwin Hai, David Ron, Wendy L. Frankel, Jean Buteau, Gary J. Kociba, Dan Lu, Tala Shukri, Matthew G. Hartman, Shane T. Grey, Marc Prentki, Denis C. Guttridge, Mi Lyang Kim, Xiaozhong Wang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Activating transcription factor Apoptosis Mice Transgenic Biology CREB Proinflammatory cytokine Islets of Langerhans Mice Stress Physiological Internal medicine Diabetes Mellitus medicine Animals Insulin Protein kinase A Cell Growth and Development Pancreas Molecular Biology Transcription factor Mice Knockout ATF3 Activating Transcription Factor 3 Cell Biology Glucagon medicine.disease Cell biology Endocrinology Gene Expression Regulation biology.protein Cytokines Signal transduction Insulitis Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 24:5721-5732 |
| ISSN: | 1098-5549 |
| Popis: | Activating transcription factor 3 (ATF3) is a stress-inducible gene and encodes a member of the ATF/CREB family of transcription factors. However, the physiological significance of ATF3 induction by stress signals is not clear. In this report, we describe several lines of evidence supporting a role of ATF3 in stress-induced beta-cell apoptosis. First, ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate. Second, induction of ATF3 is mediated in part by the NF-kappaB and Jun N-terminal kinase/stress-activated protein kinase signaling pathways, two stress-induced pathways implicated in both type 1 and type 2 diabetes. Third, transgenic mice expressing ATF3 in beta cells develop abnormal islets and defects secondary to beta-cell deficiency. Fourth, ATF3 knockout islets are partially protected from cytokine- or nitric oxide-induced apoptosis. Fifth, ATF3 is expressed in the islets of patients with type 1 or type 2 diabetes, and in the islets of nonobese diabetic mice that have developed insulitis or diabetes. Taken together, our results suggest ATF3 to be a novel regulator of stress-induced beta-cell apoptosis. |
| Databáze: | OpenAIRE |
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