title: Evidence for involvement of uncoupling proteins in cerebral mitochondrial oxidative phosphorylation deficiency of rats exposed to 5,000 m high altitude.
abstract: 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.
authors.affiliation: Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Sha-Ping-Ba District, Chongqing 400038, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.forename: Jun-Ze
authors.initials: JZ
authors.lastname: Liu
mesh_terms: D000532:Altitude Sickness / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D054022:Cerebrum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics
chemical_list: D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C492125:Slc25a14 protein, rat; C494853:Slc25a27 protein, rat