論文 - 詳細
| RRC ID | 63205 |
|---|---|
| 著者 | Kobayashi Y, Oguro A, Yagi E, Mitani A, Kudoh SN, Imaoka S. |
| タイトル | Bisphenol A and rotenone induce S-nitrosylation of protein disulfide isomerase (PDI) and inhibit neurite outgrowth of primary cultured cells of the rat hippocampus and PC12 cells. |
| ジャーナル | J Toxicol Sci |
| Abstract |
Bisphenol A (BPA) interferes the function and development of the central nervous system (CNS), resulting in behavioral abnormalities and memory loss. S-nitrosylation of protein disulfide isomerase (PDI) is increased in brains with sporadic Alzheimer's disease and Parkinson's disease. The aim of the present study was to clarify the role of nitric oxide (NO) in BPA-induced neurotoxicity. Since rotenone induces NO-mediated neurodegeneration through S-nitrosylation of PDI, it was used as a positive control. First, rats were treated with BPA and rotenone, and S-nitrosylation of PDI was detected in rat brain microsomes. BPA and rotenone decreased RNase oxidation activity of PDI concomitant with S-nitrosylation of PDI. Next, to clarify S-nitrosylation of PDI by BPA and rotenone in rat brains, we treated the rat pheochromocytoma cell line PC12 and primary cultured neuron cells from the rat hippocampus with BPA (5 and 10 μM) and rotenone (100 or 200 nM). BPA induced S-nitrosylation of PDI, while NG-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, exerted the opposite effects. Finally, to evaluate the toxicity of BPA in the CNS, we investigated its effects on neurite outgrowth of PC12 and primary cultured neuron cells. BPA inhibited neurite outgrowth of these cells, while L-NMMA reversed this inhibition. The involvement of PDI activity in neurite outgrowth was also examined, and bacitracin, a PDI inhibitor, is shown to decrease neurite outgrowth. Furthermore, the overexpression of PDI, but not a catalytically inactive PDI mutant, enhanced neurite outgrowth. These results suggested that S-nitrosylation of PDI induced by excessive NO caused BPA-induced neurotoxicity. |
| 巻・号 | 45(12) |
| ページ | 783-794 |
| 公開日 | 2020-1-1 |
| DOI | 10.2131/jts.45.783 |
| PMID | 33268678 |
| MeSH | Animals Benzhydryl Compounds / toxicity* Brain / metabolism* Depression, Chemical Hippocampus / cytology* Male Neuronal Outgrowth / drug effects* Neurotoxins* Nitric Oxide / physiology Oxidation-Reduction / drug effects PC12 Cells Phenols / toxicity* Protein Disulfide-Isomerases / metabolism* Rats Rats, Sprague-Dawley Ribonucleases / metabolism Rotenone / toxicity* omega-N-Methylarginine / pharmacology |
| IF | 1.737 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |