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Synergistic upregulation of NONO and PSPC 1 regulates Sertoli cell response to MEHP via modulation of ALDH 1A1 signaling
Author(s) -
Dong Bingwei,
Jin Xiaohang,
Yan Changyou,
Yang Tian,
Cai Guoqing,
Lu Jian
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12568
Subject(s) - microbiology and biotechnology , downregulation and upregulation , sertoli cell , biology , signal transduction , alternative splicing , chemistry , gene isoform , endocrinology , biochemistry , gene , spermatogenesis
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.