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

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 Hipoxia de altitude. Um estimulo indutor de alteracoes na homeostasia redox Apos considerar evidencias da hipoxia hipobarica enquanto um estimulo particular indutor de alteracoes deleterias a nivel sistemico, tecidual e celular, a presente breve revisao focar-se-a sobre os principais mecanismos associados a producao adicional de especies reactivas de oxigenio e nitrogenio (ERON) em humanos e animais submetidos a condicoes ambientais de hipoxia. Em oposicao aos conceitos pioneiros, a diminuicao da disponibilidade de oxigenio que se verifica em condicoes de hipoxia hipobarica e uma condicao favoravel a perda da homeostasia redox celular resultando num incremento do stress oxidativo, o qual nao e agravado apos periodos de reoxigenacao. Esta aparente condicao paradoxal de geracao adicional de radicais livres e regulada por mecanismos celulares especificos, sendo as mitocondrias fontes e simultaneamente alvos das ERON, bem como organelos criticos associados a morte celular mediada por apoptose. Palavras-chave: hipoxia, radicais livres, lesao oxidativa, mitocondrias, apoptose 4. revista (164pp):miolo 30/12/08 14:08 Page 459