Correlation between attenuation of protein disulfide isomerase activity through S-mercuration and neurotoxicity induced by methylmercury
| Autor: | Kento Makino, Tadashi Nishiya, Masatake Fujimura, Takashi Uehara, Eisuke Sugino, Yoshito Kumagai, Takashi Toyama, Takao Iwawaki, Kosaku Okuda |
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| Rok vydání: | 2014 |
| Předmět: |
Cell Survival
Protein Disulfide-Isomerases Toxicology Nitric oxide chemistry.chemical_compound Cell Line Tumor medicine Humans Viability assay RNA Messenger Protein disulfide-isomerase chemistry.chemical_classification Dose-Response Relationship Drug General Neuroscience Endoplasmic reticulum Neurotoxicity Methylmercury Compounds medicine.disease Endoplasmic Reticulum Stress Cell biology Enzyme chemistry Biochemistry Unfolded protein response Target protein Oligopeptides Transcription Factor CHOP |
| Zdroj: | Neurotoxicity research. 27(2) |
| ISSN: | 1476-3524 |
| Popis: | Methylmercury (MeHg), an environmental pollutant, causes neuronal death via endoplasmic reticulum (ER) stress; however, the precise mechanism is not fully understood. The aim of this study was to elucidate the possible mechanism of MeHg-induced neurotoxicity. Treatment with MeHg resulted in a loss of cell viability in a concentration-dependent manner accompanying the expression of ER stress marker genes in human neuroblastoma SH-SY5Y cells. We next attempted to identify a target protein for MeHg in the ER. MeHg covalently modified protein disulfide isomerase (PDI), which is important for disulfide bond formation in nascent proteins in the ER lumen. S-Nitrosylation of the catalytic domains of PDI by nitric oxide was attenuated up to 50 % by a MeHg challenge in cells. The MeHg-modified C-terminal catalytic domain in PDI was detected by MALDI-TOF/MS. Furthermore, treatment with MeHg significantly attenuated the enzymatic activity of PDI. Taken together, these observations suggest that MeHg results in ER stress and following the unfolded protein response pathway via ER dysfunction due to S-mercuration of the C-terminus of PDI. |
| Databáze: | OpenAIRE |
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