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Title 

p-Terphenyl curtisians protect cultured neuronal cells against glutamate neurotoxicity via iron chelation

Authors 

In Kyoung LeeBong Sik YunJong Pyung KimWon Gon KimIn Ja RyooS K OhY H KimIck Dong Yoo

Publisher 

Georg Thieme Verlag

Issue Date 

2003

Citation 

Planta Medica, vol. 69, no. 6, pp. 513-517

Keywords 

curtisiansglutamate neurotoxicityiron chelatormushroompaxillaceaepaxillus curtisii1,1 diphenyl 2 picrylhydrazyl4 terphenylcurtisian derivativealpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acidhydrogen peroxide

Abstract 

The hyperactivity of ionotropic glutamate receptors has been implicated in the development of the neuronal cell death seen in many neurodegenerative processes including ischemic stroke, traumatic brain injury, and epilepsy. Thus neuronal protection against glutamate-induced neurotoxicity is considered as an appropriate therapeutic strategy for preventing and treating neurodegenerative diseases. Whilst searching for blockers of glutamate-induced toxicity in mouse cortical cells, we isolated p-terphenyl curtisians A - D from the mushroom Paxillus curtisii. Curtisians protected cortical neurons from glutamate-induced toxicity in a dose-dependent manner. Among the glutamate receptor subtypes, curtisians were found to block NMDA receptor-mediated but not AMPA/kainate-mediated cell death. In addition, we found that curtisians exhibited potent antioxidative activity against iron-mediated oxidative damage which was generated by H2O2 neurotoxocity and lipid peroxidation, but no activity was detected in the superoxide, DPPH and ABTS radical scavenging systems, and in protection of N18-RE-105 cells subjected to glutamate-induced glutathione depletion. This effect was likely due to the iron chelating properties of curtisians. The iron chelation ability of curtisians was then further investigated on DNA single strand breakage (SSB) induced by the addition of iron and H2O2, and curtisians prevented DNA SSB like the iron chelator desferrioxamine. These results suggest that the neuroprotective action of curtisians is dependent on their ability to chelate iron as well as to block the NMDA receptor, and that in this context curtisians may be useful as neuroprotective agents against neurological disorders which result in neuronal cell death.

ISSN 

0032-0943

Link 

http://dx.doi.org/10.1055/s-2003-40650

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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