Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism
| Autor: | Sigurd Lenzen, Leticia Prates Roma, Mariana S. Araujo, Anna Karenina Azevedo-Martins, C Hahn, Priscila Praxedes-Garcia, Mariana Papaléo Rosim, E P Portioli-Sanches, Ewa Gurgul-Convey, M M R Valle, Viviane Abreu Nunes |
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| Přispěvatelé: | Universidade de São Paulo (USP), Universidade Federal de São Paulo (UNIFESP), Hannover Med Sch |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Cell Survival Endocrinology Diabetes and Metabolism Apoptosis progesterone Biology insulin-producing cells medicine.disease_cause chemistry.chemical_compound Endocrinology Western blot Pregnancy Dichlorofluorescein Insulin-Secreting Cells Internal medicine medicine Animals oxidative stress Rats Wistar Cells Cultured Progesterone Cell Proliferation medicine.diagnostic_test Estriol Endoplasmic reticulum apoptosis oestriol PROGESTERONA Rats Blot Diabetes Gestational chemistry DNA fragmentation Female gestational diabetes Oxidative stress Signal Transduction |
| Zdroj: | Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1530/joe-13-0202 |
| Popis: | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As b-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves b-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 mM), in the presence or absence of a-tocopherol (40 mM). After 24 or 48 h, membrane integrity andDNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. the involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2', 7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary b-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with a-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesteronetreated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic b-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone. Univ São Paulo, Sch Arts Sci & Humanities, São Paulo, Brazil Univ São Paulo, Inst Biomed Sci, São Paulo, Brazil Universidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil Hannover Med Sch, Inst Clin Biochem, Hannover, Germany Universidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil FAPESP: 05607/2007 Web of Science |
| Databáze: | OpenAIRE |
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