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Metallocorroles as cytoprotective agents against oxidative and nitrative stress in cellular models of neurodegeneration
Author(s) -
Kupershmidt Lana,
Okun Zoya,
Amit Tamar,
Mandel Silvia,
Saltsman Irena,
Mahammed Atif,
BarAm Orit,
Gross Zeev,
Youdim Moussa B. H.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06619.x
Subject(s) - oxidative stress , corrole , neuroprotection , chemistry , neurotoxicity , neurodegeneration , neurotoxin , peroxynitrite , oxidative phosphorylation , reactive oxygen species , nitration , biochemistry , neuroblastoma , pharmacology , biophysics , microbiology and biotechnology , biology , toxicity , medicine , cell culture , photochemistry , superoxide , enzyme , genetics , disease , organic chemistry
J. Neurochem. (2010) 113 , 363–373. Abstract 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.