In:
FEBS Open Bio, Wiley, Vol. 8, No. 4 ( 2018-04), p. 692-701
Abstract:
Mitochondrial uncoupling protein‐2 ( UCP 2) 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‐ iPLA 2γ) cleaves FA s from the IMM and has been shown to acts in synergy with UCP 2. Here, we tested the mechanism of mt‐ iPLA 2γ‐dependent UCP 2‐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‐ iPLA 2 γ function by the selective inhibitor R‐bromoenol lactone (R‐ BEL ) or by removing UCP 2 by genetic ablation. We found that the basal levels of protein carbonyls in lung and spleen tissues and isolated mitochondria were higher in UCP 2‐knockout mice relative to the wild‐type (wt) controls. The administration of R‐ BEL increased protein carbonyl levels in wt but not in UCP 2‐knockout ( UCP 2‐ KO ) mice. LPS further increased the protein carbonyl levels in UCP 2‐ KO mice, which correlated with protein carbonyl levels determined in wt mice treated with R‐ BEL . These results are consistent with the UCP 2/mt‐ iPLA 2 γ antioxidant mechanisms in these tissues and support the existence of UCP 2‐synergic mt‐ iPLA 2 γ‐dependent cytoprotective mechanism in vivo .
Type of Medium:
Online Resource
ISSN:
2211-5463
,
2211-5463
DOI:
10.1002/feb4.2018.8.issue-4
DOI:
10.1002/2211-5463.12410
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2651702-4
