PKCδ inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment

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

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30 Citations (Scopus)

Abstract

The present study was designed to evaluate the specific role of protein kinase C (PKC) δ in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKCδ expression, while rottlerin, a PKCδ inhibitor, significantly attenuates MA-induced hyperthermia and behavioral deficits. These behavioral effects were not significantly observed in PKCδ antisense oligonucleotide (ASO)-treated- or PKCδ knockout (-/-)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKCδ (-/-)-mice. The administration of MA also results in a significant decrease of TH phosphorylation at ser 40, but not ser 31, while the inhibition of PKCδ consistently and significantly attenuates MA-induced reduction in the phosphorylation of TH at ser 40. Therefore, these results suggest that the MA-induced enhancement of PKCδ expression is a critical factor in the impairment of TH phosphorylation at ser 40 and that pharmacological or genetic inhibition of PKCδ may be protective against MA-induced dopaminergic neurotoxicity in vivo.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalNeurochemistry International
Volume59
Issue number1
DOIs
Publication statusPublished - 01-08-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    Shin, E. J., Duong, C. X., Nguyen, X. K. T., Bing, G., Bach, J. H., Park, D. H., Nakayama, K., Ali, S. F., Kanthasamy, A. G., Cadet, J. L., Nabeshima, T., & Kim, H. C. (2011). PKCδ inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment. Neurochemistry International, 59(1), 39-50. https://doi.org/10.1016/j.neuint.2011.03.022