METALLOCORROLES AS CYTOPROTECTIVE AGENTS AGAINST OXIDATIVE AND NITRATIVE STRESS IN CELLULAR MODELS OF NEURODEGENERATION.

METALLOCORROLES AS CYTOPROTECTIVE AGENTS AGAINST OXIDATIVE AND NITRATIVE STRESS IN CELLULAR MODELS OF NEURODEGENERATION.

J Neurochem. 2010 Jan 24;

Authors: Kupershmidt L, Okun Z, Amit T, Mandel S, Saltsman I, Mahammed A, Bar-Am O, Gross Z, Youdim MB

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 (SIN-1) or the parkinsonism-related neurotoxin 6-hydroxydopamine (6-OHDA). The neuronal survival effect is further reflected by the prevention of SIN-1-induced protein nitration, inhibition of caspase-3 activation, as well as attenuation of 6-OHDA-mediated decrease in growth associated protein (GAP)-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.

PMID: 20096090 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20096090&dopt=Abstract

Posted 26 Jan 2010 4:51 AM by pubmed: neuroblastoma
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