Protective effect of the SOD/catalase mimetic MnTMPyP on inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuronal-glial cultures.
Reactive oxygen species (ROS) produced by activated microglia are deleterious to neurons. In this study, we studied the effect of Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase/catalase mimetic, on the lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons in rat mesencephalic neuroglia cultures. MnTMPyP exhibited a significantly protective effect against LPS (5 ng/ml)-induced neurotoxicity as determined by [3H]dopamine uptake and immunocytochemical analysis. MnTMPyP significantly attenuated LPS-induced production of superoxide free radical and prostaglandin E(2) (PGE(2)) in microglia. These results indicate that MnTMPyP may potentially be used for the treatment of inflammation-related degenerative neurological disorders.
Wang
Tongguang
T
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Liu
Bin
B
Qin
Liya
L
Wilson
Belinda
B
Hong
Jau Shong
JS
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D018716:Molecular Mimicry; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D014316:Tritium; D013481:Superoxides; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D002374:Catalase; D013482:Superoxide Dismutase; D015232:Dinoprostone; D004298:Dopamine