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Title of Journal: Cell Stress and Chaperones

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Abbravation: Cell Stress and Chaperones

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Springer Netherlands

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DOI

10.1002/pca.1125

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1466-1268

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Involvement of molecular chaperones and the transcription factor Nrf2 in neuroprotection mediated by para-substituted-4,5-diaryl-3-thiomethyl-1,2,4-triazines

Authors: Fariba Khodagholi, Niloufar Ansari, Mohsen Amini, Solaleh Khoramian Tusi,

Publish Date: 2012/01/04
Volume: 17, Issue:4, Pages: 409-422
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Abstract

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.


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