Dong Bing-Wei, Jin Xiao-Hang, Yan Chang-You, Yang Tian, Cai Guo-Qing, Lu Jian
Department of Pathology, Xian Yang Central Hospital, China.
Department of Histology and Embryology, Fourth Military Medical University, Xi'an, China.
FEBS Lett. 2017 Mar;591(6):914-923. doi: 10.1002/1873-3468.12568. Epub 2017 Mar 7.
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.
果蝇行为/人类剪接蛋白家族的成员，包括富含脯氨酸/谷氨酰胺的剪接因子（SFPQ）、含非POU结构域的八聚体结合蛋白（NONO）和副斑点蛋白成分1（PSPC1），在睾丸支持细胞（SCs）中大量表达，但其作用仍不清楚。在这里，我们表明，用一种著名的支持细胞毒物邻苯二甲酸单（2-乙基己基）酯（MEHP）处理，可选择性地刺激NONO和PSPC1的表达水平。同时抑制支持细胞中NONO和PSPC1的表达会增强MEHP诱导的氧化应激并加剧支持细胞死亡。从机制上讲，NONO和PSPC1通过协同结合Aldh1a1启动子中独特的CCGGAGTC序列，转录激活醛脱氢酶1（Aldh1a1）。总之，NONO/PSPC1-ALDH1A1级联反应可能是支持细胞抵御MEHP损伤不可或缺的防御机制。
