Metallocorroles as cytoprotective agents against oxidative and nitrative stress in cellular models of neurodegeneration.
Water-soluble iron, and manganese(III) complexes of corroles and porphyrins were examined with regard to their neuroprotective/neurorescue activities by using various neuronal cytotoxic models of oxidative and nitrative stress. The present study demonstrates that the metallocorroles significantly protect human neuroblastoma SH-SY5Y and mouse motor neuron-neuroblastoma fusion NSC-34 cell lines against neurotoxicity induced by either the peroxynitrite donor 3-morpholinosydnonimine or the parkinsonism-related neurotoxin 6-hydroxydopamine. The neuronal survival effect is further reflected by the prevention of 3-morpholinosydnonimine-induced protein nitration, inhibition of caspase 3 activation, as well as attenuation of 6-hydroxydopamine-mediated decrease in growth associated protein-43 levels. The iron(III) corrole, but not manganese (III) corrole, also significantly promotes neuronal survival of hydrogen peroxide (H(2)O(2))-impaired SH-SY5Y and NSC-34 cells. A substantial superiority of the metallocorroles relative to the corresponding porphyrin complexes is revealed in all examined aspects. These results highlight the large potential of corrole complexes as novel agents for therapeutic approaches in degenerative disorders of the central and peripheral nervous systems, where oxidative and nitrative stresses are involved.
Kupershmidt
Lana
L
Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Faculty of Medicine, Rappaport Family Research Institute, Technion - Israel Institute of Technology, Haifa, 31096, Israel.
Okun
Zoya
Z
Amit
Tamar
T
Mandel
Silvia
S
Saltsman
Irena
I
Mahammed
Atif
A
Bar-Am
Orit
O
Gross
Zeev
Z
Youdim
Moussa B H
MB
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects*; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D009566:Nitrates; D011166:Porphyrins; D013565:Sympatholytics; C002385:linsidomine; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D008981:Molsidomine; D053148:Caspase 3