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Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan
Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan
Graduate Institute of Basic Medicine, Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang District, New Taipei City 24205, Taiwan
School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang District, New Taipei City 24205, Taiwan
* Author to whom correspondence should be addressed.
Received: 20 June 2012; in revised form: 11 July 2012 / Accepted: 16 July 2012 / Published: 20 July 2012
Abstract: 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 Ca2+ entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting that some steps after Ca2+ 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.
Keywords: curcumin; glutamate exocytotic machinery; ERK; synapsin I; prefrontocortical nerve terminals
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Lin, T.Y.; Lu, C.W.; Huang, S.K.; Wang, S.J. Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization. Int. J. Mol. Sci. 2012, 13, 9097-9109.
Lin TY, Lu CW, Huang SK, Wang SJ. Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization. International Journal of Molecular Sciences. 2012; 13(7):9097-9109.
Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Su Jane. 2012. "Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization." Int. J. Mol. Sci. 13, no. 7: 9097-9109.