Evidence for Involvement of Uncoupling Proteins in Cerebral Mitochondrial Oxidative Phosphorylation Deficiency of Rats Exposed to 5,000 m High Altitude

• Published in: Neurochemical research 2013-02, Vol.38 (2), p.282-289
• Main Authors: Xu, Yu, Liu, Yuliang, Xia, Chen, Gao, Pan, Liu, Jun-ze
• Format: Article
• Language: English
• Subjects: Altitude Sickness - genetics; Altitude Sickness - pathology; Altitude Sickness - physiopathology; Animals; ATP; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cerebrum - metabolism; Cerebrum - pathology; Cerebrum - physiopathology; Fatty Acids, Nonesterified - physiology; Gene Expression Regulation - genetics; Ion Channels - genetics; Ion Channels - physiology; Male; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - physiology; Mitochondrial Proteins - genetics; Mitochondrial Proteins - physiology; Mitochondrial Uncoupling Proteins; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurochemistry; Neurology; Neurosciences; Original Paper; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; Up-Regulation - genetics
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-012-0917-8

The present study aimed to investigate the change of proton leak and discuss the role of cerebral uncoupling proteins (UCPs) and its regulatory molecules non-esterified fatty acid (NEFA) in high altitude mitochondrial oxidative phosphorylation deficiency. The model group animals were exposed to acute high altitude hypoxia, and the mitochondrial respiration, protein leak, UCPs abundance/activity and cerebral NEFA concentration were measured. We found that in the model group, cerebral mitochondrial oxidative phosphorylation was severely impaired with decreased ST3 respiration rate and ATP pool. Proton leak kinetics curves demonstrated an increase in proton leak; GTP binding assay pointed out that total cerebral UCPs activity significantly increased; Q-PCR and western blot showed upregulated expression of UCP4 and UCP5. Moreover, cerebral NEFA concentration increased. In conclusion, UCPs mediated proton leak is closely related to cerebral mitochondria oxidative phosphorylation deficiency during acute high altitude hypoxia and NEFA is involved in this signaling pathway.