Hypoxia impairs metabolic functions by decreasing activity and expression of ATP-consuming processes. To separate hypoxia from systemic effects, we tested whether hypoxia at high altitude affects basal and PMA-stimulated leukocyte metabolism and how this compares to acute (15 min) and 24 h of in vitro hypoxia. Leukocytes were prepared at low altitude and 24 h after arrival at 4559 m. Mitochondrial oxygen consumption (JO2 ) was measured by respirometry, oxygen radicals by electron spin resonance spectroscopy, both at a PO2 100 mmHg (JO 2,100) and 20 mmHg (JO2,20 ). Acute hypoxia of leukocytes decreased JO 2 at low altitude. Exposure to high altitude decreased JO 2,100, whereas JO2,20 was not affected. Acute hypoxia of lowaltitude samples decreased the activity of complexes I, II, and III. At high altitude, activity of complexes I and III were decreased when measured in normoxia. Stimulation of leukocytes with PMA increased JO 2,100 at low (twofold) and high altitude (five-fold). At both locations, PMA-stimulated JO 2 was decreased by acute hypoxia. Basal and PMA-stimulated reactive oxygen species (ROS) production were unchanged at high altitude. Separate in vitro experiments performed at low altitude show that 75% of PMA-induced increase in JO2 was due to increased extra-mitochondrial JO 2 (JO2,res ; in the presence of rotenone and antimycin A). JO 2,res was doubled by PMA. Acute hypoxia decreased basal JO 2,res by 70% and PMA-stimulated JO 2, res by about 50% in cells cultured in normoxia and hypoxia (1.5% O2 ; 24 h). Conversely, 24 h in vitro hypoxia decreased mitochondrial JO 2,100 and JO 2,20, extra-mitochondrial, basal, and PMA-stimulated JO2 were not affected. These results show that 24 h of high altitude but not 24h in vitro hypoxia decreased basal leukocyte metabolism, whereas PMA-induced JO 2 and ROS formation were not affected, indicating that prolonged high-altitude hypoxia impairs mitochondrial metabolism but does not impair respiratory burst. In contrast, acute hypoxia impairs respiratory burst at either altitude.
|Tudalennau (o-i)||R32 - R39|
|Cyfnodolyn||American Journal of Physiology - Regulatory, Integrative and Comparative Physiology|
|Dynodwyr Gwrthrych Digidol (DOIs)|
|Statws||Cyhoeddwyd - 20 Hyd 2010|