Synergistic upregulation of NONO and PSPC 1 regulates Sertoli cell response to MEHP via modulation of ALDH 1A1 signaling

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 ( PSPC 1), are abundantly expressed in testicular Sertoli cells ( SC s), but t...

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Published in:FEBS letters 2017-03, Vol.591 (6), p.914-923
Main Authors: Dong, Bing‐wei, Jin, Xiao‐hang, Yan, Chang‐you, Yang, Tian, Cai, Guo‐qing, Lu, Jian
Format: Article
Language:English
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Summary: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 ( PSPC 1), are abundantly expressed in testicular Sertoli cells ( SC s), 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 PSPC 1. Simultaneous inhibition of NONO and PSPC 1 expression in SC s enhances MEHP ‐induced oxidative stress and potentiates SC death. Mechanistically, NONO and PSPC 1 transcriptionally activate aldehyde dehydrogenase 1 ( Aldh1a1 ), by synergistically binding to the distinct CCGGAGTC sequence in the Aldh1a1 promoter. Together, the NONO / PSPC 1‐ ALDH 1A1 cascade may serve as an indispensable defense mechanism against MEHP insult in SC s.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12568