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Silencing of Hsp90 Chaperone Expression Protects Against 6-Hydroxydopamine Toxicity in PC12 Cells

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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.

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Acknowledgments

This work was supported financially by Iran National Science Foundation (INSF, grant number 90001703).

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Authors and Affiliations

  1. Department of Genetic and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Behrang Alani & Rasoul Salehi

  2. Department of Applied Cell Science, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran

    Behrang Alani

  3. NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Payam Sadeghi, Fariba Khodagholi & Hadi Digaleh

  4. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Payam Sadeghi, Fariba Khodagholi & Hadi Digaleh

  5. Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Zare

  6. Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Zare

  7. Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran

    Ehsan Arefian

  8. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Mazdak Ganjalikhani Hakemi

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  1. Behrang Alani
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Correspondence to Behrang Alani.

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Alani, B., Salehi, R., Sadeghi, P. et al. Silencing of Hsp90 Chaperone Expression Protects Against 6-Hydroxydopamine Toxicity in PC12 Cells. J Mol Neurosci 52, 392–402 (2014). https://doi.org/10.1007/s12031-013-0163-9

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  • DOI: https://doi.org/10.1007/s12031-013-0163-9

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