Journal
NEUROSCIENCE LETTERS
Volume 521, Issue 1, Pages 76-81Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2012.05.063
Keywords
Chrysotoxine; MPP+; Rotenone; Mitochondrial dysfunctions; NF-kappa B; Akt
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Funding
- University of Hong Kong [201007160006, 201011159206]
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Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal Dendrobium species. We previously reported that chrysotoxine structure-specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death. Whether chrysotoxine and other structurally similar bibenzyl compounds could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP+) and rotenone has not been investigated. We showed herein that chrysotoxine inhibited MPP+, but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as indexed by the decrease in membrane potential, increase in calcium concentration and NF-kappa B activation triggered by MPP+ were blocked by chrysotoxine pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3, ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3 beta) induced by MPP+ was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-kappa B modulation and regulation of multiple signals determining cell survival and cell death were involved in the protective effects of chrysotoxine against MPP+ toxicity in SH-SY5Y cells. Given the different toxic profiles of 6-OHDA and MPP+ as compared to rotenone, our results also indicated that DAT inhibition may partially account for the neuroprotective effects of chrysotoxine. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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