Hypoxia-related lipid peroxidation: evidences, implications and approaches.
Hypoxia may be intensified by concurrent oxidative stress. Lack of oxygen in relation to aerobic ATP requirements, as hypoxia has been defined, goes along with an increased generation of reactive oxygen species (ROS). Polyunsaturated fatty acids (PUFAs) range among the molecules most susceptible to ROS. Oxidative breakdown of n-3 PUFAs may compromise not only membrane lipid matrix dynamics, and hence structure and function of membrane-associated proteins like enzymes, receptors, and transporters, but also gene expression. Eicosapentaenoic acid depletion, products of lipid peroxidation (LP), as well as, lack of oxygen may combine in exacerbating activity of nuclear factor kappa B (NFkappaB), an ubiquitous pro-inflammatory and anti-apoptotic transcription factor. Field studies at high altitude show malondialdehyde (MDA) content in exhaled breath condensate (EBC) of mountaineers to correlate with Lake Louis score of acute mountain sickness. A pathogenic role of LP in hypoxia can therefore be expected. By control of LP, some species seem to cope more efficiently than others with naturally occurring hypoxia. Limitation of potential pro-inflammatory effects of hypoxia-related LP by an adequate provision of n-3 PUFAs and antioxidants may contribute to increase survival under conditions where oxygen is lacking in relation to aerobic ATP requirements. A need for antioxidant intervention, however, should be weighed against the ROS requirement for triggering adaptive processes in response to an increased demand of oxygen.
Laboratorio de Ambientes Extremos, Programa de Fisiología y Biofísica, ICBM, Facultad de Medicina, Universidad de Chile Independencia 1027, Independencia, Santiago, Chile. cbehn@med.uchile.cl
Claus
C
Behn
Oscar F
OF
Araneda
Aníbal J
AJ
Llanos
Gloria
G
Celedón
Gustavo
G
González
D000064:Acclimatization / Q000502:physiology*; D000531:Altitude; D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D017382:Reactive Oxygen Species