期刊
NEUROLOGICAL RESEARCH
卷 36, 期 1, 页码 53-64出版社
MANEY PUBLISHING
DOI: 10.1179/1743132813Y.0000000267
关键词
6-Hydroxydopamine; Protein kinase C; Subtype delta; Extracellular signal-regulated kinases (ERK); Parkinson's disease; Apoptosis; Rottlerin
资金
- International Cooperation Project of Science and Technology Department of Heilongjiang Province, China [WB08B05]
- Science and Technology Foundation of Education Department of Heilongjiang Province, China [11521076]
Objectives: The incidence of Parkinson's disease (PD) is increasing as the global population ages. 6-hydroxydopamine (6-OHDA) can induce PD-like neuropathology and biochemical changes in both in vitro and in vivo models. Therefore, clarification of the molecular mechanism of 6-OHDA-induced cell death might contribute to the understanding of the pathogenesis of PD. Methods: With this goal in mind, we investigated the role of protein kinase C delta (PKC delta) in 6-OHDA-dependent death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA to induce toxicity with or without pretreatment using rottlerin (a PKC delta inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Go 6976 (a PKC inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12-myristate- 13-acetate (PMA, a PKC activator). Results: Phorbol-12-myristate-13-acetate decreased cell survival and increased the rate of apoptosis while rottlerin increased cell survival and decreased the rate of apoptosis. In contrast, neither bisindolylmaleimide I nor Go 6976 affected 6-OHDA-induced cell death. Western analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as extracellular signal-regulated kinase (ERK) phosphorylation increased after exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta and ERK phosphorylation. Conclusion: These data suggest that PKC delta, rather than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA-induced neurotoxicity in PC12 cells, and PKC delta activity is required for subsequent ERK activation during cell death.
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