Dual effects of different concentrations of alpha-synuclein on the neurotoxicity of 6-hydroxydopamine in SH-SY5Y cells.
- Author:
Ming ZHOU
1
;
Sheng-Li XU
;
Biao CHEN
Author Information
1. Department of Neurobiology, Institute of Geriatrics of Beijing, Xuanwu Hospital of the Capital University of Medical Sciences, Key Laboratory for Neurodegenerative Disease of Ministry of Education, China.
- Publication Type:Journal Article
- MeSH:
Acetylcysteine;
analogs & derivatives;
Apoptosis;
Cell Survival;
Cells, Cultured;
Dose-Response Relationship, Drug;
Humans;
Neurons;
drug effects;
Neuroprotective Agents;
pharmacology;
Neurotoxins;
adverse effects;
Oxidopamine;
adverse effects;
Parkinson Disease;
alpha-Synuclein;
adverse effects;
pharmacology
- From:
Acta Physiologica Sinica
2009;61(4):324-330
- CountryChina
- Language:Chinese
-
Abstract:
α-synuclein (α-SN) has been postulated to play a pivotal role in the pathogenesis of Parkinson's disease (PD). However, the physiological functions of α-SN and the molecular and cellular mechanisms underlying neuronal loss remain unclear. Recent studies suggest that α-SN plays dual roles of neuroprotection and neurotoxicity depending on its concentration or level of expression. In the present study, we explored the potential mechanisms for α-SN to regulate neuronal survival. α-SN at different concentrations (0.1 to 40 mumol/L) with or without 50 mumol/L 6-hydroxydopamine (6-OHDA) were added into the culture medium of the SH-SY5Y dopaminergic neural cells. The cell viability was measured on post-treatment day 1, 2 and 3. The activity of proteasome inhibited by α-SN was tested by a proteasome activity assay system after 2 h of α-SN treatment. According to the activity of proteasome inhibited by α-SN, the correlative dose of proteasome inhibitor--lactacystin (10 nmol/L to 5 mumol/L) with or without 50 mumol/L 6-OHDA were used and the cell viability was assayed on post-treatment day 1, 2 and 3. The results showed that α-SN played dual roles of neuroprotection and neurotoxicity depending on its concentration. At low concentration (0.1 to 5 mumol/L), α-SN promoted the proliferation and protected neurons against the neurotoxicity of 6-OHDA; in contrast, at high concentration (10 to 40 mumol/L), α-SN possessed cytotoxicity. The results of lactacystin treatment implied that the dual roles of α-SN were related to the moderate and strong inhibition of proteasome activity. The MEK1/2 specific inhibitor PD98059 completely blocked the protection of both α-SN and lactacystin, suggesting that MAPK pathway might be involved in the neuroprotection of α-SN.
