Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ

Eun Joo Shin, Chu Xuan Duong, Xuan Khanh Thi Nguyen, Zhengyi Li, Guoying Bing, Jae Hyung Bach, Dae Hun Park, Keiichi Nakayama, Syed F. Ali, Anumantha G. Kanthasamy, Jean Lud Cadet, Toshitaka Nabeshima, Hyoung Chun Kim

研究成果: Article

47 引用 (Scopus)

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This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (-/-) mice. MA-induced oxidative stress (. i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (-/-) mice. Consistent with this, MA-induced apoptosis (. i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (-/-) mice. Our results suggest that . PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity.

元の言語English
ページ(範囲)98-113
ページ数16
ジャーナルBehavioural Brain Research
232
発行部数1
DOI
出版物ステータスPublished - 15-06-2012
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

これを引用

Shin, E. J., Duong, C. X., Nguyen, X. K. T., Li, Z., Bing, G., Bach, J. H., Park, D. H., Nakayama, K., Ali, S. F., Kanthasamy, A. G., Cadet, J. L., Nabeshima, T., & Kim, H. C. (2012). Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ. Behavioural Brain Research, 232(1), 98-113. https://doi.org/10.1016/j.bbr.2012.04.001