Please use this identifier to cite or link to this item: https://scholarhub.balamand.edu.lb/handle/uob/2600
Title: Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation : studies using a mitochondria-targeted spin trap derived from a-phenyl-n-tert-butylnitrone
Authors: Murphy, Michael P.
Echtay, Karim 
Blaikie, Frances H.
Asin-Cayuela, Jordi
Cochemé, Helena M.
Green, Katherine
Buckingham, Julie A.
Taylor, Ellen R.
Hurrell, Fiona
Hughes, Gillian
Miwa, Satomi
Cooper, Christopher E.
Svistunenko, Dimitri A.
Smith, Robin A.J.
Brand, Martin D
Affiliations: Faculty of Medicine 
Issue Date: 2003
Part of: Journal of biological chemistry
Volume: 278
Start page: 48534
End page: 48545
Abstract: 
Although the physiological role of uncoupling proteins (UCPs) 2 and 3 is uncertain, their activation by superoxide and by lipid peroxidation products suggest that UCPs are central to the mitochondrial response to reactive oxygen species. We examined whether superoxide and lipid peroxidation products such as 4-hydroxy-2-trans-nonenal act independently to activate UCPs, or if they share a common pathway, perhaps by superoxide exposure leading to the formation of lipid peroxidation products. This possibility can be tested by blocking the putative reactive oxygen species cascade with selective antioxidants and then reactivating UCPs with distal cascade components. We synthesized a mitochondria-targeted derivative of the spin trap α-phenyl-N-tert-butylnitrone, which reacts rapidly with carbon-centered radicals but is unreactive with superoxide and lipid peroxidation products. [4-[4-[[(1,1-Dimethylethyl)-oxidoimino]methyl]phenoxy]butyl]triphenylphosphonium bromide (MitoPBN) prevented the activation of UCPs by superoxide but did not block activation by hydroxynonenal. This was not due to MitoPBN reacting with superoxide or the hydroxyl radical or by acting as a chain-breaking antioxidant. MitoPBN did react with carbon-centered radicals and also prevented lipid peroxidation by the carbon-centered radical generator 2,2ʹ-azobis(2-methyl propionamidine) dihydrochloride (AAPH). Furthermore, AAPH activated UCPs, and this was blocked by MitoPBN. These data suggest that superoxide and lipid peroxidation products share a common pathway for the activation of UCPs. Superoxide releases iron from iron-sulfur center proteins, which then generates carbon-centered radicals that initiate lipid peroxidation, yielding breakdown products that activate UCPs.
URI: https://scholarhub.balamand.edu.lb/handle/uob/2600
Open URL: Link to full text
Type: Journal Article
Appears in Collections:Faculty of Medicine

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