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维生素调节孕酮处理的胰腺细胞中抗氧化基因的表达:妊娠期糖尿病管理的前景

Vitamins Modulate the Expression of Antioxidant Genes in Progesterone-Treated Pancreatic Cells: Perspectives for Gestational Diabetes Management.

作者信息

Borçari Nathália Ruder, Dos Santos Jeniffer Farias, Reigado Gustavo Roncoli, Freitas Bruna Letícia, Araújo Mariana da Silva, Nunes Viviane Abreu

机构信息

Department of Biotechnology, University of Sao Paulo (USP), Sao Paulo, Brazil.

Department of Biochemistry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.

出版信息

Int J Endocrinol. 2020 Sep 15;2020:8745120. doi: 10.1155/2020/8745120. eCollection 2020.

DOI:10.1155/2020/8745120
PMID:33014046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7512066/
Abstract

Gestational diabetes (GD) is a condition defined as carbohydrate intolerance and hyperglycemia beginning in the second trimester of pregnancy, which overlaps with the progesterone exponential increase. Progesterone has been shown to cause pancreatic -cell death by a mechanism dependent on the generation of reactive oxygen species and oxidative stress. Herein, we studied the effect of this hormone on the expression of 84 genes related to oxidative stress and oxidant defense in pancreatic RINm5F cell lineage. Cells were incubated with 0.1, 1.0, or 100 M progesterone for 6 or 24 h, in the presence or absence of the vitamins E and C. Among the investigated genes, five of them had their expression increased, at least 2-fold, in two different concentrations independently of the time of incubation, or at the same concentration at the different time points, including those that encode for stearoyl-CoA desaturase 1 (), dual oxidase 1 (), glutathione peroxidase 6 (), heme oxygenase 1 (), and heat shock protein a1a (). Vitamins E and C were able to increase, in progesterone-treated cells, the expression of genes with antioxidant function such as , but decreased expression, a gene with prooxidant function. At cytoplasmic level, progesterone positively modulated and content. These results suggest that the protein encoded by these genes might protect cells against progesterone induced-oxidative damage, opening perspectives to elucidate the molecular mechanism involved in progesterone action in GD, as well as for the development of antioxidant strategies for the prevention and treatment of this disease.

摘要

妊娠期糖尿病(GD)是一种被定义为在妊娠中期开始出现的碳水化合物不耐受和高血糖症的病症,这与孕酮的指数性增加相重叠。已表明孕酮通过一种依赖于活性氧生成和氧化应激的机制导致胰腺β细胞死亡。在此,我们研究了这种激素对胰腺RINm5F细胞系中84个与氧化应激和抗氧化防御相关基因表达的影响。细胞在存在或不存在维生素E和C的情况下,分别用0.1、1.0或100μM孕酮孵育6小时或24小时。在所研究的基因中,其中五个基因的表达在两种不同浓度下至少增加了2倍,且与孵育时间无关,或者在不同时间点的相同浓度下增加,包括那些编码硬脂酰辅酶A去饱和酶1()、双氧化酶1()、谷胱甘肽过氧化物酶6()、血红素加氧酶1()和热休克蛋白a1a()的基因。维生素E和C能够在孕酮处理的细胞中增加具有抗氧化功能的基因如的表达,但降低了具有促氧化功能的基因的表达。在细胞质水平上,孕酮正向调节和的含量。这些结果表明,这些基因编码的蛋白质可能保护细胞免受孕酮诱导的氧化损伤,为阐明GD中孕酮作用的分子机制以及开发预防和治疗该疾病的抗氧化策略开辟了前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/c1f64010cbff/IJE2020-8745120.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/6dd6baaf792a/IJE2020-8745120.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/e0665f39820d/IJE2020-8745120.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/4b86ac5a4a6d/IJE2020-8745120.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/c1f64010cbff/IJE2020-8745120.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/6dd6baaf792a/IJE2020-8745120.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/04dc29edc3f6/IJE2020-8745120.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/40a36d8dba63/IJE2020-8745120.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/555180d4bc2e/IJE2020-8745120.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/6fcdffccb0c0/IJE2020-8745120.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/c402acc60215/IJE2020-8745120.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/e0665f39820d/IJE2020-8745120.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/4b86ac5a4a6d/IJE2020-8745120.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b8/7512066/c1f64010cbff/IJE2020-8745120.009.jpg

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