| 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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MedLine Citation:
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PMID: 22212523 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 H(2)O(2)-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 H(2)O(2)-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. |
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Authors:
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Fariba Khodagholi; Niloufar Ansari; Mohsen Amini; Solaleh Khoramian Tusi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-01-04 |
Journal Detail:
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Title: Cell stress & chaperones Volume: 17 ISSN: 1466-1268 ISO Abbreviation: Cell Stress Chaperones Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-06 Completed Date: 2012-10-02 Revised Date: 2013-05-22 |
Medline Journal Info:
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Nlm Unique ID: 9610925 Medline TA: Cell Stress Chaperones Country: Netherlands |
Other Details:
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Languages: eng Pagination: 409-22 Citation Subset: IM |
Affiliation:
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Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. khodagholi@sbmu.ac.ir |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Down-Regulation / drug effects Gene Expression Regulation / drug effects* HSP70 Heat-Shock Proteins / metabolism HSP90 Heat-Shock Proteins / metabolism Molecular Chaperones / metabolism* NF-E2-Related Factor 2 / metabolism* Neuroprotective Agents / chemistry, pharmacology* PC12 Cells Rats Triazines / chemistry, pharmacology* Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/HSP70 Heat-Shock Proteins; 0/HSP90 Heat-Shock Proteins; 0/Molecular Chaperones; 0/NF-E2-Related Factor 2; 0/Neuroprotective Agents; 0/Triazines |
| Comments/Corrections | |
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