Dual effects of different concentrations of alpha-synuclein on the neurotoxicity of 6-hydroxydopamine in SH-SY5Y cells / 生理学报
Acta Physiologica Sinica
;
(6): 324-330, 2009.
Article
Dans Chinois
| WPRIM
| ID: wpr-302445
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Maladie de Parkinson
/
Pharmacologie
/
Acétylcystéine
/
Survie cellulaire
/
Cellules cultivées
/
Oxidopamine
/
Apoptose
/
Neuroprotecteurs
/
Relation dose-effet des médicaments
/
Alpha-Synucléine
Limites du sujet:
Humains
langue:
Chinois
Texte intégral:
Acta Physiologica Sinica
Année:
2009
Type:
Article
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