Antioxidant activity by a synergy of redox-sensitive mitochondrial phospholipase A2 and uncoupling protein-2 in lung and spleen
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23354121
DOI
10.1016/j.biocel.2013.01.010
PII: S1357-2725(13)00020-4
Knihovny.cz E-resources
- MeSH
- Antioxidants metabolism MeSH
- Cell Respiration drug effects MeSH
- Down-Regulation drug effects MeSH
- Group VI Phospholipases A2 metabolism MeSH
- Ion Channels metabolism MeSH
- Liver cytology MeSH
- Fatty Acids metabolism MeSH
- Mitochondrial Proteins metabolism MeSH
- Mitochondria drug effects enzymology metabolism MeSH
- Mice MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress drug effects MeSH
- Hydrogen Peroxide pharmacology MeSH
- Spleen cytology MeSH
- Superoxides metabolism MeSH
- tert-Butylhydroperoxide pharmacology MeSH
- Uncoupling Protein 2 MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antioxidants MeSH
- Group VI Phospholipases A2 MeSH
- Ion Channels MeSH
- Fatty Acids MeSH
- Mitochondrial Proteins MeSH
- Hydrogen Peroxide MeSH
- Pla2g6 protein, mouse MeSH Browser
- Superoxides MeSH
- tert-Butylhydroperoxide MeSH
- Ucp2 protein, mouse MeSH Browser
- Uncoupling Protein 2 MeSH
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 H2O2-activated mitochondrial calcium-independent phospholipase A2 (mt-iPLA2). Tert-butylhydroperoxide or H2O2 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-iPLA2γ isoform. Tert-butylhydroperoxide or H2O2 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-iPLA2γ-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-iPLA2 was blocked by R-BEL and not in mitochondria from UCP2-knockout mice. Mt-iPLA2γ was alternatively activated by H2O2 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-iPLA2γ, suppresses mitochondrial superoxide production by its uncoupling action. In conclusion, H2O2-activated mt-iPLA2γ and UCP2 act in concert to protect against oxidative stress.
References provided by Crossref.org
Mitochondrial Physiology of Cellular Redox Regulations
Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes
Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling
Cytoprotective activity of mitochondrial uncoupling protein-2 in lung and spleen
Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration
