Document Detail

Effectiveness of Novel Borane-Phosphine Complexes In Inhibiting Cell Death Depends on the Source of Superoxide Production Induced by Blockade of Mitochondrial Electron Transport.
MedLine Citation:
PMID:  20532184     Owner:  NLM     Status:  Publisher    
Central neurons undergo cell death after axotomy. One of the signaling pathways for this process is oxidative modification of one or more critical sulfhydryls in association with superoxide generation within mitochondria. Agents that reduce oxidized sulfhydryls are neuroprotective of axotomized retinal ganglion cells, and we hypothesized that this occurs via reversal of the effects of mitochondrial-produced superoxide. To study this, we measured the ability of the novel borane-phosphine complex drugs bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) and (3-propionic acid methyl ester)diphenylphosphine borane complex (PB2) to inhibit the death of neuron-like RGC-5 cells induced by perturbation of the mitochondrial electron transport chain. We found that borane-phosphine complexes prevent neuronal cell death from superoxide produced by the redox-cycling agent menadione and the complex III inhibitor antimycin A, which produce superoxide towards the cytoplasm and matrix, but not the complex I inhibitor rotenone, which produces superoxide in the matrix alone. The ability of these disulfide reductants to prevent cell death may be predicted by the topology of superoxide production with respect to the mitochondrial matrix and extramitochondrial space.
Emily A Seidler; Christopher J Lieven; Alex F Thompson; Leonard A Levin
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Publication Detail:
Journal Detail:
Title:  ACS chemical neuroscience     Volume:  1     ISSN:  1948-7193     ISO Abbreviation:  -     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-8-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101525337     Medline TA:  ACS Chem Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  95-103     Citation Subset:  -    
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health.
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Grant Support
R21 EY017970-01//NEI NIH HHS; P30 EY016665-05//NEI NIH HHS; R21 EY017970-02//NEI NIH HHS; R21 EY017970-02S1//NEI NIH HHS; P30 EY016665-05//NEI NIH HHS; R21 EY017970-02//NEI NIH HHS; R21 EY017970-02S1//NEI NIH HHS

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