Synergistic upregulation of NONO and PSPC1 regulates Sertoli cell response to MEHPviamodulation of ALDH1A1 signaling
| Autor: | Jian Lu, Chang-you Yan, Xiao-hang Jin, Guo-qing Cai, Bing-wei Dong, Tian Yang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Transcriptional Activation 0301 basic medicine Protein family Immunoblotting Biophysics Biochemistry Cell Line 03 medical and health sciences Splicing factor 0302 clinical medicine Downregulation and upregulation Structural Biology Diethylhexyl Phthalate Genetics medicine Animals Humans Promoter Regions Genetic Molecular Biology Binding Sites Sertoli Cells Base Sequence biology Reverse Transcriptase Polymerase Chain Reaction Nuclear Proteins RNA-Binding Proteins Paraspeckle Cell Biology Aldehyde Dehydrogenase Sertoli cell Immunohistochemistry Molecular biology Up-Regulation DNA-Binding Proteins Mice Inbred C57BL Glutamine ALDH1A1 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis RNA splicing biology.protein Protein Binding Signal Transduction |
| Zdroj: | FEBS Letters. 591:914-923 |
| ISSN: | 0014-5793 |
| DOI: | 10.1002/1873-3468.12568 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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