Cytoprotective activity of mitochondrial uncoupling protein‐2 in lung and spleen

0489819 - FGÚ 2019 RIV GB eng J - Journal Article
Jabůrek, Martin - Ježek, Jan - Ježek, Petr
Cytoprotective activity of mitochondrial uncoupling protein‐2 in lung and spleen.
FEBS Open Bio. Roč. 8, č. 4 (2018), s. 692-701. ISSN 2211-5463. E-ISSN 2211-5463
R&D Projects: GA ČR GA15-02051S
Institutional support: RVO:67985823
Keywords : antioxidative synergy * cytoprotection * mitochondrial phospholipase iPLA2 gamma * mitochondrial uncoupling protein UCP2 * protein carbonylation
OECD category: Biochemistry and molecular biology
Impact factor: 1.959, year: 2018

Mitochondrial uncoupling protein-2 (UCP2) mediates free fatty acid (FA)-dependent H+ translocation across the inner mitochondrial membrane (IMM), which leads to acceleration of respiration and suppression of mitochondrial superoxide formation. Redox-activated mitochondrial phospholipase A2 (mt-iPLA2 gamma) cleaves FAs from the IMM and has been shown to acts in synergy with UCP2. Here, we tested the mechanism of mt-iPLA2 gamma-dependent UCP2-mediated antioxidant protection using lipopolysaccharide (LPS)-induced pro-inflammatory and pro-oxidative responses and their acute influence on the overall oxidative stress reflected by protein carbonylation in murine lung and spleen mitochondria and tissue homogenates. We provided challenges either by blocking the mt-iPLA2 gamma function by the selective inhibitor R-bromoenol lactone (R-BEL) or by removing UCP2 by genetic ablation. We found that the basal levels of protein carbonyls in lung and spleen tissues and isolated mitochondria were higher in UCP2-knockout mice relative to the wild-type (wt) controls. The administration of R-BEL increased protein carbonyl levels in wt but not in UCP2-knockout (UCP2-KO) mice. LPS further increased the protein carbonyl levels in UCP2-KO mice, which correlated with protein carbonyl levels determined in wt mice treated with R-BEL. These results are consistent with the UCP2/mt-iPLA2 gamma antioxidant mechanisms in these tissues and support the existence of UCP2-synergic mt-iPLA2 gamma-dependent cytoprotective mechanism in vivo.
Permanent Link: http://hdl.handle.net/11104/0284159