Trichostatin A Induces NAG-1 Expression and Apoptosis in Human Endometriotic Stromal Cells

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Trichostatin A increased nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells in a dose-dependent manner.

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This study investigated whether trichostatin A (TSA), a histone deacetylase inhibitor, affects nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells. Ectopic endometrial tissues from 15 patients with endometriotic cysts were used to isolate and culture HESCs, which were treated with different TSA concentrations, and NAG-1 mRNA/protein levels and apoptosis (by flow cytometry) were measured; TSA reduced cell viability and increased early and late apoptosis in a dose-dependent manner while inducing NAG-1 mRNA and protein. Small-interfering RNA knockdown experiments confirmed an association between NAG-1 expression and TSA-induced apoptosis, and addition of 5-aza-2'-deoxycytidine did not enhance TSA-induced apoptosis. This paper is centrally about endometriosis — it examines TSA-induced NAG-1 expression and apoptosis in human endometriotic stromal cells.

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Abstract

To investigate the effects of trichostatin A (TSA) on nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells (HESCs), ectopic endometrial tissues were obtained from 15 patients with endometriotic cysts who underwent cystectomy. Human endometriotic stromal cells were isolated and cultured with different concentrations of TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 messenger RNA (mRNA) and protein levels were evaluated by real-time polymerase chain reaction and Western blotting, respectively, and apoptosis was assessed by flow cytometry. Viability of HESCs was reduced in a dose-dependent manner by treatment with TSA. The percentage of early and late apoptotic HESCs was increased upon treatment with TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 mRNA and protein expression was induced in a dose-dependent manner by TSA treatment. Gene knockdown experiments using small-interfering RNA confirmed an association between NAG-1 expression and TSA-induced apoptosis. Whether effects of TSA on NAG-1 gene expression are enhanced in the presence of 5-aza-2'-deoxycytidine (5-aza-dC) are also investigated; however, TSA-induced apoptosis was unaffected by 5-aza-dC. In conclusion, TSA induced apoptosis in HESCs via induction of NAG-1 expression. These results suggest that upregulation of NAG-1 contributes to TSA-induced apoptosis in HESCs.
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YUHASpace Repository 0 993 Cited 0 times in Cited 11 times in Trichostatin A Induces NAG-1 Expression and Apoptosis in Human Endometriotic Stromal Cells - Authors - Seok Kyo Seo ; Jae Hoon Lee ; Seung Joo Chon ; Bo Hyon Yun ; Sihyun Cho ; Young Sik Choi ; Byung Seok Lee - Citation - REPRODUCTIVE SCIENCES, Vol.25(9) : 1349-1356, 2018 - Journal Title - REPRODUCTIVE SCIENCES - ISSN - 1933-7191 - Issue Date - 2018 - Keywords - NAG-1 ; apoptosis ; endometriosis ; trichostatin A - Abstract - To investigate the effects of trichostatin A (TSA) on nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells (HESCs), ectopic endometrial tissues were obtained from 15 patients with endometriotic cysts who underwent cystectomy. Human endometriotic stromal cells were isolated and cultured with different concentrations of TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 messenger RNA (mRNA) and protein levels were evaluated by real-time polymerase chain reaction and Western blotting, respectively, and apoptosis was assessed by flow cytometry. Viability of HESCs was reduced in a dose-dependent manner by treatment with TSA. The percentage of early and late apoptotic HESCs was increased upon treatment with TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 mRNA and protein expression was induced in a dose-dependent manner by TSA treatment. Gene knockdown experiments using small-interfering RNA confirmed an association between NAG-1 expression and TSA-induced apoptosis. Whether effects of TSA on NAG-1 gene expression are enhanced in the presence of 5-aza-2'-deoxycytidine (5-aza-dC) are also investigated; however, TSA-induced apoptosis was unaffected by 5-aza-dC. In conclusion, TSA induced apoptosis in HESCs via induction of NAG-1 expression. These results suggest that upregulation of NAG-1 contributes to TSA-induced apoptosis in HESCs. - Appears in Collections: - 1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers - Yonsei Authors - Seo, Seok Kyo(서석교) https://orcid.org/0000-0003-3404-0484 Yun, Bo Hyon(윤보현) https://orcid.org/0000-0001-5703-797X Lee, Byung Seok(이병석) https://orcid.org/0000-0001-6001-2079 Lee, Jae Hoon(이재훈) https://orcid.org/0000-0003-4223-1395 Chon, Seung Joo(전승주) Cho, Si Hyun(조시현) https://orcid.org/0000-0003-2718-6645 Choi, Young Sik(최영식) https://orcid.org/0000-0002-1157-4822 Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

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endometriosis

MeSH descriptors

Apoptosis Endometriosis Endometrium Growth Differentiation Factor 15 Hydroxamic Acids Protein Synthesis Inhibitors Stromal Cells Apoptosis Cell Proliferation Cell Proliferation Endometriosis Endometrium Endometrium Female Gene Expression Gene Expression Growth Differentiation Factor 15 Growth Differentiation Factor 15 Humans Hydroxamic Acids

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