Quercetin Improves the Activity of the Ubiquitin-Proteasomal System in 150Q Mutated Huntingtin-Expressing Cells but Exerts Detrimental Effects on Neuronal Survivability
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Quercetin Improves the Activity of the Ubiquitin-Proteasomal System in 150Q Mutated Huntingtin-Expressing Cells but Exerts Detrimental Effects on Neuronal
Survivability
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| Creator |
Chakraborty, J
Rajamma, U Jana, N Mohanakumar, K P |
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| Subject |
Cell Biology & Physiology
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| Description |
Quercetin, a strong free radical scavenger, is investigated
for neuroprotective effects in a Neuro 2a cell line conditionally transfected with 16Q huntingtin (Htt) and 150Q
Htt, which express the protein upon stimulation. Cells
were protected from death by a 20-mM dose of quercetin
on the second day of Htt induction, but 30–100-mM doses
of the drug caused further toxicity in both 16Q and 150Q
cells, as indicated by MTT assay and by significant reductions in the number of cells bearing neurites on the second day. A significant decrease in the number of cells
containing aggregate was seen in induced 150Q cells
treated with 20 mM but not for those treated with 40 or
50 mM quercetin up to 4 days of induction. Mutated Htt
(mHtt)-induced reduction in proteasomal activity of the
ubiquitin-proteasomal system (UPS) was significantly
attenuated by 20 mM quercetin. However, neither mitochondrial membrane potential loss nor colocalization of
20S proteasome with mHtt aggregate was corrected by
quercetin treatment. Our results imply that the neuroprotective effect of quercetin arises out of the upregulation of UPS activity, which causes a decrease in the number of mHtt aggregate-harboring cells. The increased neurotoxicity could result from the continued association of mHtt with 20S proteasome and the failure of quercetin to correct mitochondrial membrane potential loss. These results
suggest that, although quercetin at a low dose protects
against mHtt-mediated cell death, higher doses are toxic
to the cells, clearly demarcating a narrow therapeutic window for this dietary flavonoid.
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| Publisher |
John Wiley & Sons
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2357/1/JOURNAL_OF_NEUROSCIENCE_RESEARCH__V.__93___(__10_)_1581%2D1591;2015.pdf
Chakraborty, J and Rajamma, U and Jana, N and Mohanakumar, K P (2015) Quercetin Improves the Activity of the Ubiquitin-Proteasomal System in 150Q Mutated Huntingtin-Expressing Cells but Exerts Detrimental Effects on Neuronal Survivability. Journal of Neuroscience Research, 93 (10). pp. 1581-1591. ISSN 0360-4012 |
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| Relation |
http://dx.doi.org/10.1002/jnr.23618
http://www.eprints.iicb.res.in/2357/ |
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