High-altitude hypoxia. A challenging strain targeting cellular redox homeostasis

 

José Magalhães^1,2,, António Ascensão^1,2,

¹Research Centre in Physical Activity, Health and Leisure, University of Porto, Portugal

²Department of Sport Biology, Faculty of Sport, University of Porto, Portugal

 

 

ABSTRACT

After putting forward some evidence of hypobaric hypoxia as a particular stimulus causing systemic, tissue and cellular challenging strains, the present short review is focused on the current findings relating the reasoning of increased tissue generation of reactive oxygen and nitrogen species (RONS) when humans and animals organisms are exposed to high-altitude environments. In contrast to earlier concepts, hypobaric hypoxia-induced decreased physiological oxygen availability seems to be a prompt condition to cellular loss of redox homeostasis resulting in increased oxidative stress, which does not further augment upon reoxygenation. The apparently paradoxical condition of hypoxia-induced free radical production is regulated by very particular and specific cellular mechanisms, being mitochondria special sources and targets of RONS as well as critical organelles related to cellular death mediated by apoptosis.

Key-words: hypoxia, free radicals, oxidative damage, mitochondria, apoptosis

 

 

RESUMO

Hipóxia de altitude. Um estímulo indutor de alterações na homeostasia redox

Após considerar evidências da hipoxia hipobárica enquanto um estímulo particular indutor de alterações deletérias a nível sistémico, tecidual e celular, a presente breve revisão focar-se-á sobre os principais mecanismos associados à produção adicional de espécies reactivas de oxigénio e nitrogénio (ERON) em humanos e animais submetidos a condições ambientais de hipóxia. Em oposição aos conceitos pioneiros, a diminuição da disponibilidade de oxigénio que se verifica em condições de hipoxia hipobárica é uma condição favorável à perda da homeostasia redox celular resultando num incremento do stress oxidativo, o qual não é agravado após períodos de reoxigenação. Esta aparente condição paradoxal de geração adicional de radicais livres é regulada por mecanismos celulares específicos, sendo as mitocôndrias fontes e simultaneamente alvos das ERON, bem como organelos críticos associados à morte celular mediada por apoptose.

Palavras-chave: hipoxia, radicais livres, lesão oxidativa, mitocôndrias, apoptose

 

 

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CORRESPONDING AUTHOR

José Magalhães

Research Center in Physical Activity, Health and Leisure

Department of Sport Biology

Faculty of Sport Sciences, University of Porto

R. Dr. Plácido Costa, 91

4200-450 Porto

Portugal

Phone: 00-351-22-5074774

Fax: 00-351-225500689

E-mail: jmaga@fade.up.pt