Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00476991" target="_blank" >RIV/67985823:_____/17:00476991 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/17:10371294

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s11010-017-3001-5" target="_blank" >http://dx.doi.org/10.1007/s11010-017-3001-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s11010-017-3001-5" target="_blank" >10.1007/s11010-017-3001-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult

Popis výsledku v původním jazyce

Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH, 10% O2) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion. The hearts were collected either after ischemia or after reperfusion and used for protein analyses and quantitative fluorescence microscopy. The CNH resulted in increased levels of HK1 and HK2 proteins and the total HK activity after ischemia compared to corresponding normoxic group. Similarly, CNH hearts exhibited increased ischemic level of Akt protein phosphorylated on Ser473. The CNH also strengthened the interaction of HK2 with mitochondria and prevented downregulation of mitochondrial creatine kinase after reperfusion. The Bax/Bcl-2 ratio was significantly lower after I/R in CNH hearts than in normoxic ones, suggesting a lower probability of apoptosis. In conclusion, the Akt/HK2 pathway is likely to play a role in the development of a cardioprotective phenotype of CNH by preventing the detachment of HK2 from mitochondria at reperfusion period and decreases the Bax/Bcl-2 ratio during I/R insult, thereby lowering the probability of apoptosis activation in the mitochondrial compartment.

Název v anglickém jazyce

Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult

Popis výsledku anglicky

Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH, 10% O2) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion. The hearts were collected either after ischemia or after reperfusion and used for protein analyses and quantitative fluorescence microscopy. The CNH resulted in increased levels of HK1 and HK2 proteins and the total HK activity after ischemia compared to corresponding normoxic group. Similarly, CNH hearts exhibited increased ischemic level of Akt protein phosphorylated on Ser473. The CNH also strengthened the interaction of HK2 with mitochondria and prevented downregulation of mitochondrial creatine kinase after reperfusion. The Bax/Bcl-2 ratio was significantly lower after I/R in CNH hearts than in normoxic ones, suggesting a lower probability of apoptosis. In conclusion, the Akt/HK2 pathway is likely to play a role in the development of a cardioprotective phenotype of CNH by preventing the detachment of HK2 from mitochondria at reperfusion period and decreases the Bax/Bcl-2 ratio during I/R insult, thereby lowering the probability of apoptosis activation in the mitochondrial compartment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Molecular and Cellular Biochemistry

ISSN

0300-8177

e-ISSN

—

Svazek periodika

432

Číslo periodika v rámci svazku

1-2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

99-108

Kód UT WoS článku

000406651600010

EID výsledku v databázi Scopus

2-s2.0-85015045591