Publication: L-glutamate enhances methylmercury toxicity by synergistically increasing oxidative stress
Issued Date
2008-11-28
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ISSN
13478648
13478613
13478613
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2-s2.0-56649108204
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Pharmacological Sciences. Vol.108, No.3 (2008), 280-289
Suggested Citation
Sirirat Amonpatumrat, Hiroyuki Sakurai, Pattama Wiriyasermkul, Narakorn Khunweeraphong, Shushi Nagamori, Hidekazu Tanaka, Pawinee Piyachaturawat, Yoshikatsu Kanai L-glutamate enhances methylmercury toxicity by synergistically increasing oxidative stress. Journal of Pharmacological Sciences. Vol.108, No.3 (2008), 280-289. doi:10.1254/jphs.08118FP Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18826
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Title
L-glutamate enhances methylmercury toxicity by synergistically increasing oxidative stress
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Abstract
Methylmercury (MeHg) is a well-known environmental toxicant. With its lipophilic nature and high reactivity to sulfhydryl groups, it is widely distributed and accumulated in the body to damage cells. Oxidative stress is proposed as a major mechanism underlying the cytotoxic action of MeHg. In the present study, we found that L-glutamate (L-Glu) concentration-dependently increased MeHg cytotoxicity in HeLa S3 cells. The enhancement of the toxicity was accompanied by enhanced apoptosis, increased production of reactive oxygen species, and decreased glutathione level. An anti-oxidant N-acetylcysteine largely alleviated the cytotoxicity, suggesting enhanced oxidative stress behind L-Glu-elicited increase of MeHg toxicity. The effect was specific to L-Glu and L-α-aminoadipate, whereas D-Glu, L-aspartate, and D-aspartate were not effective. In addition, the cystine uptake by the cells was mostly mediated by a L-Glu/L-α-aminoadipate-sensitive amino acid transport system x C. All these results suggest that the inhibition of system x-C by L-Glu underlies the enhancement of MeHg cytotoxicity. The enhancement was highly synergistic because MeHg and L-Glu alone had little toxic effect in the conditions used. This synergism was confirmed in neural cells (neuroblastoma cell lines). It is proposed that similar mechanisms may underlie the neural toxicity of MeHg, particularly in the locality of lesions characteristic of MeHg toxicity. ©2008 The Japanese Pharmacological Society.