Involvement of molecular chaperones and the transcription factor Nrf2 in neuroprotection mediated by para-substituted-4,5-diaryl-3-thiomethyl-1,2,4-triazines
Much evidence supports that oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. Herein, we studied the compensatory/adaptive mechanisms involved in 3-thiomethyl-5,6-(diphenyl)-1,2,4-triazine and 3-thiomethyl-5,6-(dichloropheny...
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| Veröffentlicht in: | Cell stress & chaperones 2012-07, Vol.17 (4), p.409-422 |
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| creator | Khodagholi, Fariba Ansari, Niloufar Amini, Mohsen Tusi, Solaleh Khoramian |
| description | Much evidence supports that oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. Herein, we studied the compensatory/adaptive mechanisms involved in 3-thiomethyl-5,6-(diphenyl)-1,2,4-triazine and 3-thiomethyl-5,6-(dichlorophenyl)-1,2,4-triazine neuroprotection. We found that these compounds could counteract H₂O₂-induced rupture of neurite outgrowth in differentiated PC12 cells. In addition, we found that pretreatment of cells with triazine derivatives could modulate the expression of heat shock proteins Hsp70, Hsp90, and Hsp32 in H₂O₂-treated PC12 cells. These compounds could also increase nuclear level of stress sensing transcription factor, NF-E2 related factor 2, which contributes to redox homeostasis and cell survival following stress. As a result, the elevated levels of glutamylcysteine synthetase, glutathione peroxidase-1, and glutathione, as well as Superoxide dismutase and catalase, increased cellular antioxidant capacity. Studying the relation between structure and activity of these compounds will pave the way for exploiting preventive and/or therapeutic strategies for the management of oxidative stress-mediated disorders. |
| doi_str_mv | 10.1007/s12192-011-0316-0 |
| format | Article |
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Herein, we studied the compensatory/adaptive mechanisms involved in 3-thiomethyl-5,6-(diphenyl)-1,2,4-triazine and 3-thiomethyl-5,6-(dichlorophenyl)-1,2,4-triazine neuroprotection. We found that these compounds could counteract H₂O₂-induced rupture of neurite outgrowth in differentiated PC12 cells. In addition, we found that pretreatment of cells with triazine derivatives could modulate the expression of heat shock proteins Hsp70, Hsp90, and Hsp32 in H₂O₂-treated PC12 cells. These compounds could also increase nuclear level of stress sensing transcription factor, NF-E2 related factor 2, which contributes to redox homeostasis and cell survival following stress. As a result, the elevated levels of glutamylcysteine synthetase, glutathione peroxidase-1, and glutathione, as well as Superoxide dismutase and catalase, increased cellular antioxidant capacity. Studying the relation between structure and activity of these compounds will pave the way for exploiting preventive and/or therapeutic strategies for the management of oxidative stress-mediated disorders.</abstract><cop>Dordrecht</cop><pub>Springer</pub><pmid>22212523</pmid><doi>10.1007/s12192-011-0316-0</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell stress & chaperones, 2012-07, Vol.17 (4), p.409-422 |
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| subjects | Animals Antioxidants Apoptosis Biochemistry Biomedical and Life Sciences Biomedicine Blotting, Western Cancer Research Cell Biology Cellular differentiation Chromaffin cells Down-Regulation - drug effects Gene Expression Regulation - drug effects HSP70 Heat-Shock Proteins - metabolism HSP90 Heat-Shock Proteins - metabolism Immunology Molecular Chaperones - metabolism Neurites Neurons Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology Neurosciences NF-E2-Related Factor 2 - metabolism Original Paper Oxidative stress PC12 Cells Rats Reactive oxygen species Triazines Triazines - chemistry Triazines - pharmacology Up-Regulation - drug effects |
| title | Involvement of molecular chaperones and the transcription factor Nrf2 in neuroprotection mediated by para-substituted-4,5-diaryl-3-thiomethyl-1,2,4-triazines |
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