title: Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: probably an indirect action via the regulation of NFκB/FasL circuitry.
abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential "switch on" effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.
authors.affiliation: Department of Urology, 174th Hospital of PLA, Fujian 361001, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Chen
authors.forename: Yushu
authors.initials: Y
authors.lastname: Dong
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.forename: Liming
authors.initials: L
authors.lastname: Jiang
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.forename: Wugang
authors.initials: W
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002843:Chromatin / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004781:Environmental Exposure; D053222:Fas Ligand Protein / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D012097:Repressor Proteins; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D053222:Fas Ligand Protein; C503336:Mta1 protein, mouse; D016328:NF-kappa B; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate
keywords: Fas/FasL; Metastasis associated protein 1 (MTA1); Mono-(2-ethylhexyl) phthalate (MEHP); Nuclear factor-κB (NFκB); Sertoli cell