| Literature DB >> 23102218 |
Geoffrey F Kelso1, Andrej Maroz, Helena M Cochemé, Angela Logan, Tracy A Prime, Alexander V Peskin, Christine C Winterbourn, Andrew M James, Meredith F Ross, Sally Brooker, Carolyn M Porteous, Robert F Anderson, Michael P Murphy, Robin A J Smith.
Abstract
Superoxide (O(2)(·-)) is the proximal mitochondrial reactive oxygen species underlying pathology and redox signaling. This central role prioritizes development of a mitochondria-targeted reagent selective for controlling O(2)(·-). We have conjugated a mitochondria-targeting triphenylphosphonium (TPP) cation to a O(2)(·-)-selective pentaaza macrocyclic Mn(II) superoxide dismutase (SOD) mimetic to make MitoSOD, a mitochondria-targeted SOD mimetic. MitoSOD showed rapid and extensive membrane potential-dependent uptake into mitochondria without loss of Mn and retained SOD activity. Pulse radiolysis measurements confirmed that MitoSOD was a very effective catalytic SOD mimetic. MitoSOD also catalyzes the ascorbate-dependent reduction of O(2)(·-). The combination of mitochondrial uptake and O(2)(·-) scavenging by MitoSOD decreased inactivation of the matrix enzyme aconitase caused by O(2)(·-). MitoSOD is an effective mitochondria-targeted macrocyclic SOD mimetic that selectively protects mitochondria from O(2)(·-) damage.Entities:
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Year: 2012 PMID： 23102218 DOI： 10.1016/j.chembiol.2012.08.005
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521