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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00489819" target="_blank" >RIV/67985823:_____/18:00489819 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/2211-5463.12410" target="_blank" >http://dx.doi.org/10.1002/2211-5463.12410</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/2211-5463.12410" target="_blank" >10.1002/2211-5463.12410</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA15-02051S" target="_blank" >GA15-02051S: Úloha redox-sensitivní mitochondriální fosfolipázy iPLA2γ v regulaci buněčné antioxidační ochrany</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

FEBS Open Bio

ISSN

2211-5463

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

692-701

Kód UT WoS článku

000428997200019

EID výsledku v databázi Scopus

2-s2.0-85043451803