Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP+, but not rotenone, neurotoxicity in dopaminergic SH-SY5Y cells

Juxian SONG, Pang Chui Shaw, Ricky N S WONG, Cho Wing SZE, Xin Sheng Yao, Chi Wai Tang, Yao Tong, Yan Bo Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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-κB 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-3β) induced by MPP+ was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-κB 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.

Original languageEnglish
Pages (from-to)76-81
Number of pages6
JournalNeuroscience Letters
Volume521
Issue number1
DOIs
Publication statusPublished - 11 Jul 2012

Scopus Subject Areas

  • Neuroscience(all)

User-Defined Keywords

  • Akt
  • Chrysotoxine
  • Mitochondrial dysfunctions
  • NF-κB
  • Rotenone

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