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Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells.
Mol Pharmacol. 1998 Dec; 54(6):1046-54.MP

Abstract

Treatment of human neuroblastoma SH-SY5Y cells with 1 mM 1-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, N6,2'-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.

Authors+Show Affiliations

Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9855633

Citation

Kitamura, Y, et al. "Protective Effects of the Antiparkinsonian Drugs Talipexole and Pramipexole Against 1-methyl-4-phenylpyridinium-induced Apoptotic Death in Human Neuroblastoma SH-SY5Y Cells." Molecular Pharmacology, vol. 54, no. 6, 1998, pp. 1046-54.
Kitamura Y, Kosaka T, Kakimura JI, et al. Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells. Mol Pharmacol. 1998;54(6):1046-54.
Kitamura, Y., Kosaka, T., Kakimura, J. I., Matsuoka, Y., Kohno, Y., Nomura, Y., & Taniguchi, T. (1998). Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells. Molecular Pharmacology, 54(6), 1046-54.
Kitamura Y, et al. Protective Effects of the Antiparkinsonian Drugs Talipexole and Pramipexole Against 1-methyl-4-phenylpyridinium-induced Apoptotic Death in Human Neuroblastoma SH-SY5Y Cells. Mol Pharmacol. 1998;54(6):1046-54. PubMed PMID: 9855633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells. AU - Kitamura,Y, AU - Kosaka,T, AU - Kakimura,J I, AU - Matsuoka,Y, AU - Kohno,Y, AU - Nomura,Y, AU - Taniguchi,T, PY - 1998/12/18/pubmed PY - 1998/12/18/medline PY - 1998/12/18/entrez SP - 1046 EP - 54 JF - Molecular pharmacology JO - Mol Pharmacol VL - 54 IS - 6 N2 - Treatment of human neuroblastoma SH-SY5Y cells with 1 mM 1-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, N6,2'-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. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/9855633/Protective_effects_of_the_antiparkinsonian_drugs_talipexole_and_pramipexole_against_1_methyl_4_phenylpyridinium_induced_apoptotic_death_in_human_neuroblastoma_SH_SY5Y_cells_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9855633 DB - PRIME DP - Unbound Medicine ER -