PubMed ID: 20532184
Author(s): Seidler EA, Lieven CJ, Thompson AF, Levin LA. Effectiveness of novel borane-phosphine complexes in inhibiting cell death depends on the source of superoxide production induced by blockade of mitochondrial electron transport. ACS Chem Neurosci. 2010 Feb 17;1(2):95-103. PMID 20532184
Journal: Acs Chemical Neuroscience, Volume 1, Issue 2, Feb 2010
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.