Silencing of Hsp90 chaperone expression protects against 6-hydroxydopamine toxicity in PC12 cells

Alani, B. and Salehi, R. and Sadeghi, P. and Zare, M. and Khodagholi, F. and Arefian, E. and Hakemi, M.G. and Digaleh, H. (2014) Silencing of Hsp90 chaperone expression protects against 6-hydroxydopamine toxicity in PC12 cells. Journal of Molecular Neuroscience, 52 (3). pp. 392-402.

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Abstract

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder that has been shown to be associated with oxidative stress. This phenomenon occurs primarily via generation of 6-hydroxydopamine (6-OHDA) in catecholaminergic neurons leading to activation of apoptosis. The 90-kDa heat shock protein (Hsp90) functions as a chaperone in maintaining the functional stability and viability of cells under a transforming pressure. Since Hsp90 binds to inactive transcription factor heat shock factor-1 (HSF-1), inhibition of Hsp90 could activate HSF-1 and transcription of heat shock element containing genes subsequently, like Hsp70 as an anti-apoptotic factor. Our trial of silencing Hsp90 expression through transfection of Hsp90 siRNAs into neuronal PC12 cells being exposed to 6-OHDA resulted in the inhibition of pro-apoptotic factors, Bax, caspase-3, and PARP and upregulation of anti-apoptotic factor, Bcl2. In this manner, our data suggest a protective role for Hsp70 as it was observed to be induced upon Hsp90 knockdown. Furthermore, our results showed that Hsp90 silencing against 6-OHDA-induced oxidative stress may associate with upregulation of nuclear factor-erythroid 2-related factor 2. In summary, we found that silencing of Hsp90 expression leads to induction of cytoprotective pathways which can protect neurons against apoptosis in a PD model. © 2013 Springer Science+Business Media New York.

Item Type: Article
Additional Information: cited By 8
Uncontrolled Keywords: Animals; Apoptosis Regulatory Proteins; Cell Survival; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Neurons; Oxidopamine; PC12 Cells; Rats; RNA Interference; RNA, Messenger; RNA, Small Interfering
Subjects: Biochemistry, Genetics and Molecular Biology
Divisions: Faculty of Medicine > Basic Sciences > Applied Cell Sciences
Depositing User: editor . 2
Date Deposited: 05 Mar 2017 22:55
Last Modified: 05 Mar 2017 22:55
URI: http://eprints.kaums.ac.ir/id/eprint/421

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