详细记录  
题名:Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism.
作者:NUNES VA; PORTIOLI-SANCHES EP; ROSIN MP; ARAUJO MD; PRAXEDES-GARCIA P; VALLE MM; ROMA L; GURGUL-CONVEY E; HAHN C; LENZEN S; AZEVEDO-MARTINS AK;
来源:J Endocrinol. 2014 Mar 4. [ IF= 0.00 ] ]
URL :10.1530/JOE-13-0202
日期:20140408
摘要:Progesterone has been associated with gestational diabetes (GD) development due
to the enhancement of insulin resistance. Since beta-cell apoptosis participates
in type 1 and type 2 diabetes pathophysiology, we hypothesized that progesterone
might contribute to the development of GD through a mechanism that also involves
beta-cell death. To address this question, RINm5F insulin-producing cells were
incubated with progesterone (25 to 100 muM), in the presence or absence of
alpha-tocopherol (40 muM). After 24 or 48 h, membrane integrity and DNA
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 DCFDA oxidation. Isolated rat islets were used in similar
experiments in order to confirm the effect of progesterone in primary beta-cells.
Incubation of RINm5F cells with progesterone increased the number of cells with
membrane integrity loss and DNA fragmentation. Progesterone induced reactive
species generation. Pre-incubation with alpha-tocopherol attenuated
progesterone-induced apoptosis. Western blot analyses revealed an increased
expression of CREB-2 and CHOP in progesterone-treated cells. Progesterone caused
apoptotic death of rat islet cells and enhanced reactive species generation. Our
results show that progesterone can be toxic to pancreatic beta-cells through an
oxidative stress-dependent mechanism inducing apoptosis. This effect may
contribute to the development of GD during pregnancy, particularly under
conditions that require administration of pharmacological doses of this hormone.

================  评  论  部  分=================

重要性:
分类:(参照 Faculty of 1000 的分类体系)


评语:

评论密码:   返回前页  [全部]