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

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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.

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Acknowledgments

This study was supported by the National Nature Science Foundation of China (NSFC, No. 30772455). TPMP+ electrode was set up by professor Ya-Qin Chai of the Southwest University of China.

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Authors and Affiliations

  1. Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Sha-Ping-Ba District, Chongqing, 400038, China

    Yu Xu, Chen Xia, Pan Gao & Jun-ze Liu

  2. Department of Respiratory Medicine, Xin Qiao Hospital, Third Military Medical University, Chongqing, China

    Yu Xu

  3. Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Yuliang Liu

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  1. Yu Xu
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  2. Yuliang Liu
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  3. Chen Xia
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  4. Pan Gao
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  5. Jun-ze Liu
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Correspondence to Jun-ze Liu.

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Xu, Y., Liu, Y., Xia, C. et al. Evidence for Involvement of Uncoupling Proteins in Cerebral Mitochondrial Oxidative Phosphorylation Deficiency of Rats Exposed to 5,000 m High Altitude. Neurochem Res 38, 282–289 (2013). https://doi.org/10.1007/s11064-012-0917-8

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  • DOI: https://doi.org/10.1007/s11064-012-0917-8

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