Mitochondrial genome modulates myocardial Akt/Glut/HK salvage pathway in spontaneously hypertensive rats adapted to chronic hypoxia

0492482 - FGÚ 2019 RIV US eng J - Journal Article
Nedvědová, I. - Kolář, D. - Elsnicová, B. - Horníková, D. - Novotný, J. - Kalous, M. - Pravenec, Michal - Neckář, Jan - Kolář, František - Žurmanová, J.M.
Mitochondrial genome modulates myocardial Akt/Glut/HK salvage pathway in spontaneously hypertensive rats adapted to chronic hypoxia.
Physiological Genomics. Roč. 50, č. 7 (2018), s. 532-541. ISSN 1094-8341. E-ISSN 1531-2267
R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G
Institutional support: RVO:67985823
Keywords : akt pathway * cardioprotection * hypoxia * mitochondrial genome * SHR strains
OECD category: Physiology (including cytology)
Impact factor: 2.581, year: 2018

Recently we have shown that adaptation to continuous normobaric hypoxia (CNH) decreases myocardial ischemia/reperfusion injury in spontaneously hypertensive rats (SHR) and in a conplastic strain (SHR-mtBN). The protective effect was stronger in the latter group characterized by a selective replacement of the SHR mitochondrial genome with that of a more ischemia-resistant Brown Norway strain. The aim of the present study was to examine the possible involvement of the hypoxia inducible factor (HIF)-dependent pathway of the protein kinase B/glucose transporters/hexokinase (Akt/GLUT/HK) in this mitochondrial genome-related difference of the cardioprotective phenotype. Adult male rats were exposed for 3 wk to CNH (FIO2 0.1). The expression of dominant isoforms of Akt, GLUT, and HK in left ventricular myocardium was determined by real-time RT-PCR and Western blotting. Subcellular localization of GLUTs was assessed by quantitative immunofluorescence. Whereas adaptation to hypoxia markedly upregulated protein expression of HK2, GLUT1, and GLUT4 in both rat strains, Akt2 protein level was significantly increased in SHR-mtBN only. Interestingly, a higher content of HK2 was revealed in the sarcoplasmic reticulum-enriched fraction in SHR-mtBN after CNH. The increased activity of HK determined in the mitochondrial fraction after CNH in both strains suggested an increase of HK association with mitochondria. Interestingly, HIF1a mRNA increased and HIF2a mRNA decreased after CNH, the former effect being more pronounced in SHR-mtBN than in SHR. Pleiotropic effects of upregulated Akt2 along with HK translocation to mitochondria and mitochondria-associated membranes can potentially contribute to a stronger CNH-afforded cardioprotection in SHR-mtBN compared with progenitor SHR.
Permanent Link: http://hdl.handle.net/11104/0286000