The role of system Xc in methamphetamine-induced dopaminergic neurotoxicity in mice

Duy Khanh Dang, Eun Joo Shin, Hai Quyen Tran, Dae Joong Kim, Ji Hoon Jeong, Choon Gon Jang, Seung Yeol Nah, Hideyo Sato, Toshitaka Nabeshima, Yukio Yoneda, Hyoung Chun Kim

研究成果: Article

8 引用 (Scopus)

抄録

The cystine/glutamate antiporter (system Xc, Sxc) transports cystine into cell in exchange for glutamate. Since xCT is a specific subunit of Sxc, we employed xCT knockout mice and investigated whether this antiporter affected methamphetamine (MA)-induced dopaminergic neurotoxicity. MA treatment significantly increased striatal oxidative burdens in wild type mice. xCT inhibitor [i.e., S-4-carboxy-phenylglycine (CPG), sulfasalazine] or an xCT knockout significantly protected against these oxidative burdens. MA-induced increases in Iba-1 expression and Iba-1-labeled microglial immunoreactivity (Iba-1-IR) were significantly attenuated by CPG or sulfasalazine administration or xCT knockout. CPG or sulfasalazine significantly attenuated MA-induced TUNEL-positive cell populations in the striatum of Taconic ICR mice. The decrease in excitatory amino acid transporter-2 (or glutamate transporter-1) expression and increase in glutamate release were attenuated by CPG, sulfasalazine or xCT knockout. In addition, CPG, sulfasalazine or xCT knockout significantly protected against dopaminergic loss (i.e., decreases in tyrosine hydroxylase expression and immunoreactivity, and an increase in dopamine turnover rate) induced by MA. However, CPG, sulfasalazine or xCT knockout did not significantly affect the impaired glutathione system [i.e., decrease in reduced glutathione (GSH) and increase in oxidized glutathione (GSSG)] induced by MA. Our results suggest that Sxc mediates MA-induced neurotoxicity via facilitating oxidative stress, microgliosis, proapoptosis, and glutamate-related toxicity.

元の言語English
ページ(範囲)254-265
ページ数12
ジャーナルNeurochemistry International
108
DOI
出版物ステータスPublished - 09-2017

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Methamphetamine
Sulfasalazine
Glutamic Acid
Antiporters
Cystine
Glutathione Disulfide
Glutathione
Excitatory Amino Acid Transporter 2
Amino Acid Transport System X-AG
Corpus Striatum
Inbred ICR Mouse
In Situ Nick-End Labeling
Tyrosine 3-Monooxygenase
Knockout Mice
Dopamine
Oxidative Stress
Population

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

これを引用

Dang, D. K., Shin, E. J., Tran, H. Q., Kim, D. J., Jeong, J. H., Jang, C. G., ... Kim, H. C. (2017). The role of system Xc in methamphetamine-induced dopaminergic neurotoxicity in mice. Neurochemistry International, 108, 254-265. https://doi.org/10.1016/j.neuint.2017.04.013
Dang, Duy Khanh ; Shin, Eun Joo ; Tran, Hai Quyen ; Kim, Dae Joong ; Jeong, Ji Hoon ; Jang, Choon Gon ; Nah, Seung Yeol ; Sato, Hideyo ; Nabeshima, Toshitaka ; Yoneda, Yukio ; Kim, Hyoung Chun. / The role of system Xc in methamphetamine-induced dopaminergic neurotoxicity in mice. :: Neurochemistry International. 2017 ; 巻 108. pp. 254-265.
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title = "The role of system Xc− in methamphetamine-induced dopaminergic neurotoxicity in mice",
abstract = "The cystine/glutamate antiporter (system Xc−, Sxc) transports cystine into cell in exchange for glutamate. Since xCT is a specific subunit of Sxc, we employed xCT knockout mice and investigated whether this antiporter affected methamphetamine (MA)-induced dopaminergic neurotoxicity. MA treatment significantly increased striatal oxidative burdens in wild type mice. xCT inhibitor [i.e., S-4-carboxy-phenylglycine (CPG), sulfasalazine] or an xCT knockout significantly protected against these oxidative burdens. MA-induced increases in Iba-1 expression and Iba-1-labeled microglial immunoreactivity (Iba-1-IR) were significantly attenuated by CPG or sulfasalazine administration or xCT knockout. CPG or sulfasalazine significantly attenuated MA-induced TUNEL-positive cell populations in the striatum of Taconic ICR mice. The decrease in excitatory amino acid transporter-2 (or glutamate transporter-1) expression and increase in glutamate release were attenuated by CPG, sulfasalazine or xCT knockout. In addition, CPG, sulfasalazine or xCT knockout significantly protected against dopaminergic loss (i.e., decreases in tyrosine hydroxylase expression and immunoreactivity, and an increase in dopamine turnover rate) induced by MA. However, CPG, sulfasalazine or xCT knockout did not significantly affect the impaired glutathione system [i.e., decrease in reduced glutathione (GSH) and increase in oxidized glutathione (GSSG)] induced by MA. Our results suggest that Sxc mediates MA-induced neurotoxicity via facilitating oxidative stress, microgliosis, proapoptosis, and glutamate-related toxicity.",
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Dang, DK, Shin, EJ, Tran, HQ, Kim, DJ, Jeong, JH, Jang, CG, Nah, SY, Sato, H, Nabeshima, T, Yoneda, Y & Kim, HC 2017, 'The role of system Xc in methamphetamine-induced dopaminergic neurotoxicity in mice', Neurochemistry International, 巻. 108, pp. 254-265. https://doi.org/10.1016/j.neuint.2017.04.013

The role of system Xc in methamphetamine-induced dopaminergic neurotoxicity in mice. / Dang, Duy Khanh; Shin, Eun Joo; Tran, Hai Quyen; Kim, Dae Joong; Jeong, Ji Hoon; Jang, Choon Gon; Nah, Seung Yeol; Sato, Hideyo; Nabeshima, Toshitaka; Yoneda, Yukio; Kim, Hyoung Chun.

:: Neurochemistry International, 巻 108, 09.2017, p. 254-265.

研究成果: Article

TY - JOUR

T1 - The role of system Xc− in methamphetamine-induced dopaminergic neurotoxicity in mice

AU - Dang, Duy Khanh

AU - Shin, Eun Joo

AU - Tran, Hai Quyen

AU - Kim, Dae Joong

AU - Jeong, Ji Hoon

AU - Jang, Choon Gon

AU - Nah, Seung Yeol

AU - Sato, Hideyo

AU - Nabeshima, Toshitaka

AU - Yoneda, Yukio

AU - Kim, Hyoung Chun

PY - 2017/9

Y1 - 2017/9

N2 - The cystine/glutamate antiporter (system Xc−, Sxc) transports cystine into cell in exchange for glutamate. Since xCT is a specific subunit of Sxc, we employed xCT knockout mice and investigated whether this antiporter affected methamphetamine (MA)-induced dopaminergic neurotoxicity. MA treatment significantly increased striatal oxidative burdens in wild type mice. xCT inhibitor [i.e., S-4-carboxy-phenylglycine (CPG), sulfasalazine] or an xCT knockout significantly protected against these oxidative burdens. MA-induced increases in Iba-1 expression and Iba-1-labeled microglial immunoreactivity (Iba-1-IR) were significantly attenuated by CPG or sulfasalazine administration or xCT knockout. CPG or sulfasalazine significantly attenuated MA-induced TUNEL-positive cell populations in the striatum of Taconic ICR mice. The decrease in excitatory amino acid transporter-2 (or glutamate transporter-1) expression and increase in glutamate release were attenuated by CPG, sulfasalazine or xCT knockout. In addition, CPG, sulfasalazine or xCT knockout significantly protected against dopaminergic loss (i.e., decreases in tyrosine hydroxylase expression and immunoreactivity, and an increase in dopamine turnover rate) induced by MA. However, CPG, sulfasalazine or xCT knockout did not significantly affect the impaired glutathione system [i.e., decrease in reduced glutathione (GSH) and increase in oxidized glutathione (GSSG)] induced by MA. Our results suggest that Sxc mediates MA-induced neurotoxicity via facilitating oxidative stress, microgliosis, proapoptosis, and glutamate-related toxicity.

AB - The cystine/glutamate antiporter (system Xc−, Sxc) transports cystine into cell in exchange for glutamate. Since xCT is a specific subunit of Sxc, we employed xCT knockout mice and investigated whether this antiporter affected methamphetamine (MA)-induced dopaminergic neurotoxicity. MA treatment significantly increased striatal oxidative burdens in wild type mice. xCT inhibitor [i.e., S-4-carboxy-phenylglycine (CPG), sulfasalazine] or an xCT knockout significantly protected against these oxidative burdens. MA-induced increases in Iba-1 expression and Iba-1-labeled microglial immunoreactivity (Iba-1-IR) were significantly attenuated by CPG or sulfasalazine administration or xCT knockout. CPG or sulfasalazine significantly attenuated MA-induced TUNEL-positive cell populations in the striatum of Taconic ICR mice. The decrease in excitatory amino acid transporter-2 (or glutamate transporter-1) expression and increase in glutamate release were attenuated by CPG, sulfasalazine or xCT knockout. In addition, CPG, sulfasalazine or xCT knockout significantly protected against dopaminergic loss (i.e., decreases in tyrosine hydroxylase expression and immunoreactivity, and an increase in dopamine turnover rate) induced by MA. However, CPG, sulfasalazine or xCT knockout did not significantly affect the impaired glutathione system [i.e., decrease in reduced glutathione (GSH) and increase in oxidized glutathione (GSSG)] induced by MA. Our results suggest that Sxc mediates MA-induced neurotoxicity via facilitating oxidative stress, microgliosis, proapoptosis, and glutamate-related toxicity.

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