Difference between revisions of "Horscroft 2012 Abstract IOC72"
Line 1: | Line 1: | ||
{{Abstract | {{Abstract | ||
|title=Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ (2012) Mitochondrial function at altitude in lowland Europeans and highland Sherpas. Mitochondr Physiol Network 17.13. | |title=Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ (2012) Mitochondrial function at altitude in lowland Europeans and highland Sherpas. Mitochondr Physiol Network 17.13. | ||
|info=[ | |info=[http://www.oroboros.at/?IOC-dec_schroecken IOC72 Open Access] | ||
|authors=Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ | |authors=Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ | ||
|year=2012 | |year=2012 |
Revision as of 18:15, 17 December 2012
Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ (2012) Mitochondrial function at altitude in lowland Europeans and highland Sherpas. Mitochondr Physiol Network 17.13. |
Link: IOC72 Open Access
Horscroft J, Kotwica AO, Ashmore T, Colleoni F, Morash AJ, Gilbert E, Gnaiger E, Martin DS, Murray AJ (2012)
Event: IOC72
Hypoxia is a feature of many diseases including chronic obstructive pulmonary disease, anaemia and heart failure, and may play a key role in the progression of such diseases. The study of healthy humans at high altitude allows an understanding of the physiological responses to hypoxia, in the absence of confounding factors associated with disease states. Lowland Europeans acclimatising to high altitude hypoxia, have a profound loss of skeletal muscle mitochondrial density [1], complex I protein levels and CI+CII oxidative capacity [2]. The cause of such hypoxia-driven changes is not entirely understood, since a robust erythropoetic response ensures that blood oxygen content is maintained in lowlanders even up to 7000 m above sea-level. Work from our group has indicated that microcirculatory blood flow is impaired at high altitude, suggesting that limited oxygen delivery to the tissues may underlie these changes. Moreover, it is not known whether muscle mitochondrial loss occurs in Sherpas, the Nepalese highlanders of Tibetan descent who have adapted to high altitude for over 30,000 years. Tibetans are known to have elevated plasma levels of NO metabolites associated with improved blood flow [3], so we hypothesise that Sherpas will be resistant to hypoxia-driven suppression of muscle mitochondrial function. In spring 2013, we will perform high-resolution respirometry on muscle biopsies from 12 lowland Europeans and 12 Sherpas at low altitude and following sub-acute exposure to altitude on an expedition to Everest Base Camp, Nepal (5300m). Furthermore, mitochondrial function will be re-evaluated in the European population following a six week stay at altitude. LEAK, OXPHOS and ETS states will be assessed in the presence of a number of substrates and inhibitors. Respirometry will be complemented by metabolomic analyses, and levels of hypoxia-related signalling molecules and mitochondrial proteins will be measured in the same biopsies. We aim to understand how the response to high-altitude hypoxia differs between European and Sherpa populations. Such differences may explain why individual patients tolerate hypoxia differently in some disease states.
β’ Keywords: Hypoxia, High-altitude, Oxygen delivery
β’ O2k-Network Lab: UK Cambridge Murray AJ, AT Innsbruck OROBOROS
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human Tissue;cell: Skeletal muscle
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
Affiliations and author contributions
James A Horscroft, Aleksandra O Kotwica, Tom Ashmore, Francesca Colleoni, Andrea J Morash, Edward Gilbert, Erich Gnaiger, Daniel S Martin, Andrew J Murray and the Xtreme Everest Research Group
Department of Physiology, Development and Neuroscience, University of Cambridge, UK; Email: [email protected]