%0 Journal Article
%T Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization
%A Tzu Yu Lin
%A Cheng Wei Lu
%A Shu Kuei Huang
%A Su Jane Wang
%J International Journal of Molecular Sciences
%D 2012
%I MDPI AG
%R 10.3390/ijms13079097
%X Curcumin, one of the major constituents of Curcuma longa, has been shown to inhibit depolarization-evoked glutamate release from rat prefrontocortical nerve terminals by reducing voltage-dependent Ca 2+ entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting that some steps after Ca 2+ entry are regulated by curcumin. Furthermore, disrupting the cytoskeleton organization using cytochalasin D abolished the inhibitory action of curcumin on ionomycin-induced glutamate release. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of curcumin on ionomycin-induced glutamate release. Western blot analyses showed that curcumin decreased the ionomycin-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. These results show that curcumin-mediated inhibition of glutamate release involves modulating downstream events by controlling synaptic vesicle recruitment and exocytosis, possibly through a decrease of MAPK/ERK activation and synapsin I phosphorylation, thereby decreasing synaptic vesicle availability for exocytosis.
%K curcumin
%K glutamate exocytotic machinery
%K ERK
%K synapsin I
%K prefrontocortical nerve terminals
%U http://www.mdpi.com/1422-0067/13/7/9097