Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by oxidative stress in N2A cells.
1-Methyl-4-phenyl-pyridine ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a Parkinsonian syndrome in humans and animals, a neurotoxic effect postulated to derive from oxidative stress. We report here the first investigation of MPP+-induced oxidative stress in the murine neuroblastoma cell line N2A. Significant cell death was observed following exposure to 0.25 mM MPP+. Markers of oxidative stress included decreased intracellular levels of GSH after 48 h of exposure (85% depletion) as well as an increase in GSSG. Expression of both superoxide dismutase 1 (sod1) and catalase (cat) mRNA was increased, as well the activity of catalase. These cellular effects were, at least partially, reversed by treatment with the natural polyphenol mangiferin. Administration of mangiferin protected N2A cells against MPP+-induced cytotoxicity, restored the GSH content (to 60% of control levels), and down-regulated both sod1 and cat mRNA expression. Together, these results suggest that the protective effect of mangiferin in N2A cells is mediated by the quenching of reactive oxygen intermediates. Therefore, mangiferin could be a useful compound in therapies for degenerative diseases, including Parkinson's disease, in which oxidative stress plays a crucial role.
Amazzal
Laïla
L
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, FR CNRS 2843, UFR SciFA, Université Paul Verlaine-Metz, Rue du Général Delestraint, 57070 Metz, France.
Lapôtre
Agnès
A
Quignon
Frédéric
F
Bagrel
Denyse
D
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002374:Catalase / Q000235:genetics; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D044004:Xanthones; C013592:mangiferin; D007501:Iron; D002374:Catalase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione; D015655:1-Methyl-4-phenylpyridinium; D019803:Glutathione Disulfide