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Publication : Synergistic upregulation of NONO and PSPC1 regulates Sertoli cell response to MEHP via modulation of ALDH1A1 signaling.

First Author  Dong BW Year  2017
Journal  FEBS Lett Volume  591
Issue  6 Pages  914-923
PubMed ID  28117896 Mgi Jnum  J:240875
Mgi Id  MGI:5896680 Doi  10.1002/1873-3468.12568
Citation  Dong BW, et al. (2017) Synergistic upregulation of NONO and PSPC1 regulates Sertoli cell response to MEHP via modulation of ALDH1A1 signaling. FEBS Lett 591(6):914-923
abstractText  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.
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