Cabergoline protects SH-SY5Y neuronal cells in an in vitro model of ischemia.
Dopamine receptor agonists are protective in different models of neurodegeneration by both receptor-dependent and -independent mechanisms. We used SH-SY5Y cells, differentiated into neuron-like type, to evaluate if cabergoline, a dopamine D2 receptor agonist endowed with anti-oxidant activity, protects the cells against ischemia (oxygen-glucose deprivation model). Cabergoline protected the cells from ischemia-induced cell death in a concentration-dependent manner (EC(50)=1.2 microM), as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and fluorescein diacetate-propidium iodide staining. This effect, observed even when the drug was added after oxygen-glucose deprivation, was not mediated by either dopamine D2 receptor activation or anti-apoptotic Bcl-2 protein over-expression (Western blotting analysis), but was linked to a reduction in cellular free radical loading (2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining) and membrane lipid peroxidation (thiobarbituric acid-reacting test). In conclusion, cabergoline protects in vitro neurons against ischemia-induced cell death, suggesting its possible use in the therapy of other neurodegenerative diseases in addition to Parkinson's disease.
Miglio
Gianluca
G
DISCAFF Department, University of Piemonte Orientale Amedeo Avogadro, Via Bovio 6, 28100 Novara, Italy.
Varsaldi
Federica
F
Francioli
Elisabetta
E
Battaglia
Angelo
A
Canonico
Pier Luigi
PL
Lombardi
Grazia
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000077465:Cabergoline; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004873:Ergolines / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006220:Haloperidol / Q000008:administration & dosage; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D018491:Dopamine Agonists; D004873:Ergolines; D016166:Free Radical Scavengers; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D014212:Tretinoin; D005947:Glucose; D006220:Haloperidol; D000077465:Cabergoline