Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria.
Chronic hypoxia increases the myocardial resistance to acute ischemia-reperfusion injury by affecting the mitochondrial redox balance. Hexokinase (HK) bears a high potential to suppress the excessive formation of reactive oxygen species because of its increased association with mitochondria, thereby inhibiting the membrane permeability transition pore opening and preventing cell death. The purpose of this study was to determine the effect of severe intermittent hypobaric hypoxia (7,000 m, 8 h/day, 5 wk) on the function and colocalization of HK isoforms with mitochondria in the left (LV) and right ventricles of rat myocardium. The real-time RT-PCR, Western blot, enzyme coupled assay, and quantitative immunofluorescence techniques were used. Our results showed significantly elevated expression of HK isoforms (HK1 and HK2) in the hypoxic LV. In addition, intermittent hypoxia increased the total HK activity and the association of HK isoforms with mitochondria in both ventricles. These findings suggest that HK may contribute to the cardioprotective phenotype induced by adaptation to severe intermittent hypobaric hypoxia.
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and.
Petra
P
Waskova-Arnostova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and.
Barbara
B
Elsnicova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and.
Dita
D
Kasparova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and.
Daniela
D
Hornikova
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Frantisek
F
Kolar
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and.
Jiri
J
Novotny
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; and jitka.zurmanova@natur.cuni.cz.
Jitka
J
Zurmanova
D000222:Adaptation, Physiological; D000399:Air Pressure; D000818:Animals; D001835:Body Weight; D006400:Hematocrit; D006593:Hexokinase / Q000378:metabolism*; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D006593:Hexokinase
cardioprotection; chronic hypoxia; hexokinase; mitochondria colocalization; rat heart