title: Synergistic upregulation of NONO and PSPC1 regulates Sertoli cell response to MEHP via modulation of ALDH1A1 signaling.
abstract: Members of the Drosophila behavior/human splicing protein family, including splicing factor proline/glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and paraspeckle protein component 1 (PSPC1), are abundantly expressed in testicular Sertoli cells (SCs), but their roles remain obscure. Here, we show that treatment with mono-(2-ethylhexyl) phthalate (MEHP), a well-known SC toxicant, selectively stimulates the expression levels of NONO and PSPC1. Simultaneous inhibition of NONO and PSPC1 expression in SCs enhances MEHP-induced oxidative stress and potentiates SC death. Mechanistically, NONO and PSPC1 transcriptionally activate aldehyde dehydrogenase 1 (Aldh1a1), by synergistically binding to the distinct CCGGAGTC sequence in the Aldh1a1 promoter. Together, the NONO/PSPC1-ALDH1A1 cascade may serve as an indispensable defense mechanism against MEHP insult in SCs.
authors.affiliation: Department of Pathology, Xian Yang Central Hospital, China.
authors.forename: Bing-Wei
authors.initials: BW
authors.lastname: Dong
authors.affiliation: Department of Histology and Embryology, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiao-Hang
authors.initials: XH
authors.lastname: Jin
authors.affiliation: Xi'an Health Management Service Center, China.
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Yan
authors.affiliation: Department of Histology and Embryology, Fourth Military Medical University, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, Xian Yang Central Hospital, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C500331:Nono protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C494389:paraspeckle protein 1, mouse; D004051:Diethylhexyl Phthalate; D000444:Aldehyde Dehydrogenase; C016599:mono-(2-ethylhexyl)phthalate
keywords: 
  DBHS
  ; 
  MEHP
  ; ALDH1A1; Sertoli cell; transcription activator