Sesamin modulates tyrosine hydroxylase, superoxide dismutase, catalase, inducible NO synthase and interleukin-6 expression in dopaminergic cells under MPP+-induced oxidative stress.
Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP(+)) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP(+)-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP(+)-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP(+) stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP(+)-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.
Lahaie-Collins
Vicky
V
Department of Biochemistry, Neuroscience Research Group, Université du Québec, Trois-Rivières, Québec, Canada.
Bournival
Julie
J
Plouffe
Marilyn
M
Carange
Julie
J
Martinoli
Maria-Grazia
MG
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000096:biosynthesis* / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000378:metabolism
D000975:Antioxidants; D004149:Dioxoles; D050483:Dopamine Plasma Membrane Transport Proteins; D015850:Interleukin-6; D017705:Lignans; D017382:Reactive Oxygen Species; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D015655:1-Methyl-4-phenylpyridinium; C054125:sesamin; D004298:Dopamine