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Abstract #26463 Published in IGR 12-3
Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy
Kanamori A; Catrinescu M-M; Mahammed A; Gross Z; Levin LAJournal of Neurochemistry 2010; 114: 488-498
Corroles are tetrapyrrolic macrocycles that have come under increased attention because of their unique capabilities for oxidation catalysis, reduction catalysis, and biomedical applications. Corrole-metal complexes (metallocorroles) can decompose certain reactive oxygen species (ROS), similar to metalloporphyrins. We investigated whether Fe-, Mn-, and Ga-corroles have neuroprotective effects on neurons and correlated this with superoxide scavenging activity in vitro and in vivo. Apoptosis was induced in retinal ganglion cell-5 neuronal precursor cells by serum deprivation. Cell death was measured with sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate and calcein-AM/propidium iodide assays. Fe- and Mn-corroles, but not the non-redox-active Ga-corrole used as control, reduced RGC-5 cell death after serum deprivation. Serum deprivation caused increased levels of intracellular superoxide, detected by an increase in the fluorescence intensity of 2-hydroxyethidium, and this was blocked by Fe- and Mn-corroles, but not Ga-corrole. In vivo real-time confocal imaging of retinas after optic nerve transection assessed the superoxide production within individual rat retinal ganglion cells. Fe- and Mn-corroles, but not Ga-corrole, scavenged neuronal superoxide in vivo. Given that the neuroprotective activity of metallocorroles correlated with superoxide scavenging activity, Fe- and Mn-corroles could be candidate drugs for delaying neuronal death after axonal injury in optic neuropathies, such as glaucoma.
L. A. Levin. Maisonneuve-Rosemont Hospital, 5415 boul. de lAssomption, Montreal, QC H1T 2M4, Canada. lalevin@facstaff.wisc.edu
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
