Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death
| Autor: | Lorella M.T. Canzoniero, Giusy Laudati, Gianfranco Di Renzo, Mario Galgani, Maria Triassi, Marianna Santopaolo, Luigi Formisano, Paolo Montuori, Natascia Guida |
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| Přispěvatelé: | Guida, N, Laudati, G, Galgani, M, Santopaolo, M, Montuori, Paolo, Triassi, Maria, DI RENZO, GIANFRANCO MARIA LUIGI, Canzoniero, Lm, Formisano, L. |
| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
endocrine system Proteasome Endopeptidase Complex SH-SY5Y Cell Survival Biology Toxicology Histone Deacetylases chemistry.chemical_compound Ubiquitin Cell Line Tumor Diethylhexyl Phthalate medicine Animals Humans Rats Wistar Pharmacology DEHP MC-1568 Cell Death Dose-Response Relationship Drug Phthalate Ubiquitination HDAC4 Acetylation Cell biology Rats Histone Deacetylase Inhibitors Repressor Proteins Trichostatin A chemistry Biochemistry Apoptosis biology.protein medicine.drug |
| Zdroj: | Toxicology and applied pharmacology 280 (2014): 190–198. doi:10.1016/j.taap.2014.07.014 info:cnr-pdr/source/autori:Guida, Natascia; Laudati, Giusy; Galgani, Mario; Santopaolo, Marianna; Montuori, Paolo; Triassi, Maria; Di Renzo, Gianfranco; Canzoniero, Lorella M. T.; Formisano, Luigi/titolo:Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl) phthalate (DEHP), determining neuronal death/doi:10.1016%2Fj.taap.2014.07.014/rivista:Toxicology and applied pharmacology/anno:2014/pagina_da:190/pagina_a:198/intervallo_pagine:190–198/volume:280 |
| ISSN: | 1096-0333 |
| DOI: | 10.1016/j.taap.2014.07.014 |
| Popis: | Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1-100 mu M) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. (C) 2014 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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