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Antioxidant activity by a synergy of redox-sensitive mitochondrial phospholipase A2 and uncoupling protein-2 in lung and spleen.
MedLine Citation:
PMID:  23354121     Owner:  NLM     Status:  Publisher    
Mitochondrial uncoupling protein-2 (UCP2) has been suggested to participate in the attenuation of the reactive oxygen species production, but the mechanism of action and the physiological significance of UCP2 activity remain controversial. Here we tested the hypothesis that UCP2 provides feedback downregulation of oxidative stress in vivo via synergy with an H(2)O(2)-activated mitochondrial calcium-independent phospholipase A(2) (mt-iPLA(2)). Tert-butylhydroperoxide or H(2)O(2) induced free fatty acid release from mitochondrial membranes as detected by gas chromatography/mass spectrometry, which was inhibited by r-bromoenol lactone (r-BEL) but not by its stereoisomer s-BEL, suggesting participation of mt-iPLA(2)γ isoform. Tert-butylhydroperoxide or H(2)O(2) also induced increase in respiration and decrease in mitochondrial membrane potential in lung and spleen mitochondria from control but not UCP2-knockout mice. These data suggest that mt-iPLA(2)γ-dependent release of free fatty acids promotes UCP2-dependent uncoupling. Upon such uncoupling, mitochondrial superoxide formation decreased instantly also in the s-BEL presence, but not when mt-iPLA(2) was blocked by r-BEL and not in mitochondria from UCP2-knockout mice. Mt-iPLA(2)γ was alternatively activated by H(2)O(2) produced probably in conjunction with the electron-transferring flavoprotein:ubiquinone oxidoreductase (ETFQOR), acting in fatty acid β-oxidation. Palmitoyl-d,l-carnitine addition to mouse lung mitochondria, respiring with succinate plus rotenone, caused a respiration increase that was sensitive to r-BEL and insensitive to s-BEL. We thus demonstrate for the first time that UCP2, functional due to fatty acids released by redox-activated mt-iPLA(2)γ, suppresses mitochondrial superoxide production by its uncoupling action. In conclusion, H(2)O(2)-activated mt-iPLA(2)γ and UCP2 act in concert to protect against oxidative stress.
Martin Jabůrek; Jan Ježek; Jaroslav Zelenka; Petr Ježek
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  -     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ltd.
Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences, Vídeňská 1083, Prague, 14220 Czech Republic.
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