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	Yu Xu, Yuliang Liu, Chen Xia, Pan Gao, Jun-Ze Liu
Journal	Neurochemical research (Neurochem Res) Vol. 38 Issue 2 Pg. 282-9 (Feb 2013) ISSN: 1573-6903 [Electronic] United States
PMID	23266757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Fatty Acids, Nonesterified Ion Channels Mitochondrial Membrane Transport Proteins Mitochondrial Proteins Mitochondrial Uncoupling Proteins Nerve Tissue Proteins RNA, Messenger Slc25a14 protein, rat Slc25a27 protein, rat
Topics	Altitude Sickness (genetics, pathology, physiopathology) Animals Cerebrum (metabolism, pathology, physiopathology) Fatty Acids, Nonesterified (physiology) Gene Expression Regulation (genetics) Ion Channels (genetics, physiology) Male Mitochondria (metabolism, pathology) Mitochondrial Diseases (genetics, metabolism, pathology) Mitochondrial Membrane Transport Proteins (genetics, physiology) Mitochondrial Proteins (genetics, physiology) Mitochondrial Uncoupling Proteins Nerve Tissue Proteins (genetics, physiology) RNA, Messenger (biosynthesis) Random Allocation Rats Rats, Sprague-Dawley Up-Regulation (genetics)

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