Tunicamycin enhances the apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand in endometriotic stromal cells

A. Hasegawa, Akiko Hasegawa, Yutaka Osuga, Yasushi Hirota, Koji Hamasaki, Kahori Hamasaki, Ako Kodama, A. Kodama, Mutsuo Harada, Miyuki Harada, Toshiki Tajima, T. Tajima, Y. Takemura, Yuri Takemura, Tetsuya Hirata, Osamu Yoshino, Kaori Koga, T. Yano, Tetsu Yano, Yojiro Taketani, Yuji Taketani
Human Reproduction · 2008 · vol. 24(2) , pp. 408–414 · doi:10.1093/humrep/den385 · PMID:18978361 · W2120585880
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Tunicamycin increased DR5 mRNA and TRAIL-induced apoptosis in endometriotic stromal cells, an effect inhibited by a caspase inhibitor and DR5 siRNA.

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Abstract

BACKGROUND: The increase in concentration of osteoprotegerin, an antagonist of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the peritoneal fluid of women with endometriosis may interfere with TRAIL-induced apoptosis in endometriotic cells and promote the development of endometriosis. In the present study, the effect of tunicamycin, a possible apoptosis enhancer, on TRAIL-induced apoptosis in endometriotic stromal cells (ESC) was determined. METHODS: ESC were isolated from cyst walls of ovarian endometrioma and cultured. ESC were incubated with or without tunicamycin (2 microg/ml) for the first 16 h, and then incubated with or without TRAIL (200 ng/ml) for the following 24 h. To examine whether caspases were involved in TRAIL-induced apoptosis, z-VAD-fmk (30 microM), a general caspase inhibitor, was added 1 h before TRAIL treatment. ESC were transfected with small interfering RNA (siRNA) for DR5, a receptor of TRAIL, before tunicamycin treatment to evaluate its role in ESC. DR5 mRNA level was determined by quantitative RT-PCR. Apoptosis in ESC was evaluated by flow cytometry. RESULTS: Tunicamycin increases both DR5 mRNA (P < 0.005) and TRAIL-induced apoptosis (P < 0.0001) in ESC. The increase in TRAIL-induced apoptosis in ESC by tunicamycin was suppressed (P < 0.05) by z-VAD-fmk. Transfection with DR5 siRNA suppressed the tunicamycin-induced increase in DR5 mRNA and abrogated the up-regulation of TRAIL-induced apoptosis by tunicamycin. CONCLUSIONS: The combined treatment with tunicamycin and TRAIL may have therapeutic potential in the treatment of endometriosis.

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Condition tags

endometriosisendometrioma

MeSH descriptors

Anti-Bacterial Agents Apoptosis Endometriosis Stromal Cells TNF-Related Apoptosis-Inducing Ligand Tunicamycin Anti-Bacterial Agents Apoptosis Cells, Cultured Endometriosis Female Gene Expression Gene Expression Humans Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, TNF-Related Apoptosis-Inducing Ligand RNA Interference RNA, Messenger RNA, Messenger

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