Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37696 http://dx.doi.org/10.1530/JOE-13-0202 |
Resumo: | 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. |
id |
UFSP_6e271ddc571c913851b1ddc3e9bc328a |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/37696 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Nunes, V. A.Portioli-Sanches, E. P.Rosim, M. P.Araujo, M. S. [UNIFESP]Praxedes-Garcia, P. [UNIFESP]Valle, M. M. R.Roma, L. P.Hahn, C.Gurgul-Convey, E.Lenzen, S.Azevedo-Martins, A. K.Universidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Hannover Med Sch2016-01-24T14:37:10Z2016-01-24T14:37:10Z2014-05-01Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 221, n. 2, p. 273-284, 2014.0022-0795http://repositorio.unifesp.br/handle/11600/37696http://dx.doi.org/10.1530/JOE-13-020210.1530/JOE-13-0202WOS:000337110900014Progesterone 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Arts Sci & Humanities, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilHannover Med Sch, Inst Clin Biochem, Hannover, GermanyUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 05607/2007Web of Science273-284engBioscientifica LtdJournal of Endocrinologyinsulin-producing cellsprogesteroneoestriolapoptosisoxidative stressgestational diabetesProgesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanisminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/376962022-07-08 10:58:19.383metadata only accessoai:repositorio.unifesp.br:11600/37696Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:58:19Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
title |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
spellingShingle |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism Nunes, V. A. insulin-producing cells progesterone oestriol apoptosis oxidative stress gestational diabetes |
title_short |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
title_full |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
title_fullStr |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
title_full_unstemmed |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
title_sort |
Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism |
author |
Nunes, V. A. |
author_facet |
Nunes, V. A. Portioli-Sanches, E. P. Rosim, M. P. Araujo, M. S. [UNIFESP] Praxedes-Garcia, P. [UNIFESP] Valle, M. M. R. Roma, L. P. Hahn, C. Gurgul-Convey, E. Lenzen, S. Azevedo-Martins, A. K. |
author_role |
author |
author2 |
Portioli-Sanches, E. P. Rosim, M. P. Araujo, M. S. [UNIFESP] Praxedes-Garcia, P. [UNIFESP] Valle, M. M. R. Roma, L. P. Hahn, C. Gurgul-Convey, E. Lenzen, S. Azevedo-Martins, A. K. |
author2_role |
author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) Hannover Med Sch |
dc.contributor.author.fl_str_mv |
Nunes, V. A. Portioli-Sanches, E. P. Rosim, M. P. Araujo, M. S. [UNIFESP] Praxedes-Garcia, P. [UNIFESP] Valle, M. M. R. Roma, L. P. Hahn, C. Gurgul-Convey, E. Lenzen, S. Azevedo-Martins, A. K. |
dc.subject.eng.fl_str_mv |
insulin-producing cells progesterone oestriol apoptosis oxidative stress gestational diabetes |
topic |
insulin-producing cells progesterone oestriol apoptosis oxidative stress gestational diabetes |
description |
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. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-05-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:37:10Z |
dc.date.available.fl_str_mv |
2016-01-24T14:37:10Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 221, n. 2, p. 273-284, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37696 http://dx.doi.org/10.1530/JOE-13-0202 |
dc.identifier.issn.none.fl_str_mv |
0022-0795 |
dc.identifier.doi.none.fl_str_mv |
10.1530/JOE-13-0202 |
dc.identifier.wos.none.fl_str_mv |
WOS:000337110900014 |
identifier_str_mv |
Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 221, n. 2, p. 273-284, 2014. 0022-0795 10.1530/JOE-13-0202 WOS:000337110900014 |
url |
http://repositorio.unifesp.br/handle/11600/37696 http://dx.doi.org/10.1530/JOE-13-0202 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Endocrinology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
273-284 |
dc.publisher.none.fl_str_mv |
Bioscientifica Ltd |
publisher.none.fl_str_mv |
Bioscientifica Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764157628448768 |