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Research ArticleArticle

Protective Effects of the Antiparkinsonian Drugs Talipexole and Pramipexole against 1-Methyl-4-phenylpyridinium-Induced Apoptotic Death in Human Neuroblastoma SH-SY5Y Cells

Yoshihisa Kitamura, Tadashi Kosaka, Jun-Ichi Kakimura, Yasuji Matsuoka, Yasuko Kohno, Yasuyuki Nomura and Takashi Taniguchi
Molecular Pharmacology December 1998, 54 (6) 1046-1054; DOI: https://doi.org/10.1124/mol.54.6.1046
Yoshihisa Kitamura
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Tadashi Kosaka
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Jun-Ichi Kakimura
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Yasuji Matsuoka
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Yasuko Kohno
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Yasuyuki Nomura
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Takashi Taniguchi
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Abstract

Treatment of human neuroblastoma SH-SY5Y cells with 1 mm1-methyl-4-phenylpyridinium (MPP+) for 3 days induced production of reactive oxygen species (ROS), followed by caspase-3 activation, cleavage of poly(ADP-ribose) polymerase (PARP), and apoptotic cell death with DNA fragmentation and characteristic morphological changes (condensed chromatin and fragmented nuclei). Simultaneous treatment with 1 mm talipexole slightly inhibited the MPP+-induced ROS production and apoptotic cell death. In contrast, pretreatment with 1 mm talipexole for 4 days markedly protected the cells against MPP+-induced apoptosis. However, this protective effect might not be mediated by dopamine receptors. The talipexole pretreatment induced an increase in antiapoptotic Bcl-2 protein level but had no effect on levels of proapoptotic Bax, Bak, and Bad. It also inhibited MPP+-induced ROS production, p53 expression, and cleavages of caspase-3 and PARP. Similarly, pramipexole pretreatment increased Bcl-2 and inhibited MPP+-induced apoptosis. Although pretreatment with bromocriptine also had a protective effect against MPP+-induced apoptosis, it had no effect on the protein levels of Bcl-2 family members. On the other hand,N 6,2′-O-dibutyryl cAMP or calphostin C induced a decreased Bcl-2 level and enhanced MPP+-induced cell death. These results suggest that talipexole has dual actions: (1) it directly scavenges ROS, affording slight protection against MPP+-induced apoptosis, and (2) it induces Bcl-2 expression, thereby affording more potent protection, if it is administrated before MPP+. Pramipexole has similar effects, whereas bromocriptine seems to exhibit the former but not the latter effect.

Footnotes

    • Received April 28, 1998.
    • Accepted August 28, 1998.
  • Send reprint requests to: Takashi Taniguchi, Ph.D., Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan. E-mail:taniguti{at}mb.kyoto-phu.ac.jp

  • This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture in Japan (Y. Ki, Y.M., Y.N., T.T.).

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 54 (6)
Molecular Pharmacology
Vol. 54, Issue 6
1 Dec 1998
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Research ArticleArticle

Protective Effects of the Antiparkinsonian Drugs Talipexole and Pramipexole against 1-Methyl-4-phenylpyridinium-Induced Apoptotic Death in Human Neuroblastoma SH-SY5Y Cells

Yoshihisa Kitamura, Tadashi Kosaka, Jun-Ichi Kakimura, Yasuji Matsuoka, Yasuko Kohno, Yasuyuki Nomura and Takashi Taniguchi
Molecular Pharmacology December 1, 1998, 54 (6) 1046-1054; DOI: https://doi.org/10.1124/mol.54.6.1046

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Research ArticleArticle

Protective Effects of the Antiparkinsonian Drugs Talipexole and Pramipexole against 1-Methyl-4-phenylpyridinium-Induced Apoptotic Death in Human Neuroblastoma SH-SY5Y Cells

Yoshihisa Kitamura, Tadashi Kosaka, Jun-Ichi Kakimura, Yasuji Matsuoka, Yasuko Kohno, Yasuyuki Nomura and Takashi Taniguchi
Molecular Pharmacology December 1, 1998, 54 (6) 1046-1054; DOI: https://doi.org/10.1124/mol.54.6.1046
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