Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine

Linqing Ma, Yasumasa Ohyagi, Norimichi Nakamura, Kyoko M. Iinuma, Katsue Miyoshi, Eri Himeno, Naoko Soejima, Yuki T. Yanagihara, Nobutaka Sakae, Ryo Yamasaki, Jun-Ichi Kira

Research output: Contribution to journalArticle

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Abstract

Apomorphine hydrochloride (APO) is known to be a dopamine receptor agonist, and has recently been found to be a novel drug for Alzheimer's disease (AD). We found that APO treatment ameliorated oxidative stress in an AD mouse model and specifically attenuated the hydrogen peroxide-induced p53-related apoptosis in the SH-SY5Y neuroblastoma cell line. To further understand the mechanism behind this action, we investigated the actions of APO on intracellular redox systems, such as the glutathione cycle and catalase. We studied the effects of specific inhibitors for glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (BCNU, MCS, and ATZ, respectively) on the effects of APO. Treatments with MCS or BCNU, but not ATZ, significantly attenuated the protective effects of APO. Interestingly, APO treatment elevated GPx activity, but did not increase the expression of the GPx1 protein. Although BCNU treatment attenuated APO effects, GR activity was not elevated by APO treatment. The same effects were observed in primary neuronal cultures. In addition, treatment with dopamine D1, D2, D3 and D4 receptor antagonists did not counteract the protective action of APO. Thus, APO may enhance GPx activity through dopamine receptor-independent pathways.

Original languageEnglish
Pages (from-to)225-237
Number of pages13
JournalJournal of Alzheimer's Disease
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

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Apomorphine
Glutathione Peroxidase
Apoptosis
Carmustine
Glutathione Reductase
Catalase
Alzheimer Disease
Dopamine D4 Receptors
Inhibition (Psychology)
Dopamine D1 Receptors
Dopamine D2 Receptors
Dopamine Agonists
Dopamine Receptors
Neuroblastoma
Hydrogen Peroxide
Oxidation-Reduction
Glutathione
Oxidative Stress
Cell Line

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine. / Ma, Linqing; Ohyagi, Yasumasa; Nakamura, Norimichi; Iinuma, Kyoko M.; Miyoshi, Katsue; Himeno, Eri; Soejima, Naoko; Yanagihara, Yuki T.; Sakae, Nobutaka; Yamasaki, Ryo; Kira, Jun-Ichi.

In: Journal of Alzheimer's Disease, Vol. 27, No. 1, 01.01.2011, p. 225-237.

Research output: Contribution to journalArticle

Ma, L, Ohyagi, Y, Nakamura, N, Iinuma, KM, Miyoshi, K, Himeno, E, Soejima, N, Yanagihara, YT, Sakae, N, Yamasaki, R & Kira, J-I 2011, 'Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine', Journal of Alzheimer's Disease, vol. 27, no. 1, pp. 225-237. https://doi.org/10.3233/JAD-2011-110140
Ma, Linqing ; Ohyagi, Yasumasa ; Nakamura, Norimichi ; Iinuma, Kyoko M. ; Miyoshi, Katsue ; Himeno, Eri ; Soejima, Naoko ; Yanagihara, Yuki T. ; Sakae, Nobutaka ; Yamasaki, Ryo ; Kira, Jun-Ichi. / Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine. In: Journal of Alzheimer's Disease. 2011 ; Vol. 27, No. 1. pp. 225-237.
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