title: Preparation for oxidative stress under hypoxia and metabolic depression: Revisiting the proposal two decades later.
abstract: Organisms that tolerate wide variations in oxygen availability, especially to hypoxia, usually face harsh environmental conditions during their lives. Such conditions include, for example, lack of food and/or water, low or high temperatures, and reduced oxygen availability. In contrast to an expected strong suppression of protein synthesis, a great number of these animals present increased levels of antioxidant defenses during oxygen deprivation. These observations have puzzled researchers for more than 20 years. Initially, two predominant ideas seemed to be irreconcilable: on one hand, hypoxia would decrease reactive oxygen species (ROS) production, while on the other the induction of antioxidant enzymes would require the overproduction of ROS. This induction of antioxidant enzymes during hypoxia was viewed as a way to prepare animals for oxidative damage that may happen ultimately during reoxygenation. The term "preparation for oxidative stress" (POS) was coined in 1998 based on such premise. However, there are many cases of increased oxidative damage in several hypoxia-tolerant organisms under hypoxia. In addition, over the years, the idea of an assured decrease in ROS formation under hypoxia was challenged. Instead, several findings indicate that the production of ROS actually increases in response to hypoxia. Recently, it became possible to provide a comprehensive explanation for the induction of antioxidant enzymes under hypoxia. The supporting evidence and the limitations of the POS idea are extensively explored in this review as we discuss results from research on estivation and situations of low oxygen stress, such as hypoxia, freezing exposure, severe dehydration, and air exposure of water-breathing animals. We propose that, under some level of oxygen deprivation, ROS are overproduced and induce changes leading to hypoxic biochemical responses. These responses would occur mainly through the activation of specific transcription factors (FoxO, Nrf2, HIF-1, NF-κB, and p53) and post translational mechanisms, both mechanisms leading to enhanced antioxidant defenses. Moreover, reactive nitrogen species are candidate modulators of ROS generation in this scenario. We conclude by drawing out the future perspectives in this field of research, and how advances in the knowledge of the mechanisms involved in the POS strategy will offer new and innovative study scenarios of biological and physiological cellular responses to environmental stress.
authors.affiliation: Laboratório de Radicais Livres, Departamento de Biologia Celular, Universidade de Brasília, Brasí;lia, DF, 70910-900, Brazil. Electronic address: hermes.unb@gmail.com.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Hermes-Lima
authors.affiliation: Laboratório de Radicais Livres, Departamento de Biologia Celular, Universidade de Brasília, Brasí;lia, DF, 70910-900, Brazil.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Moreira
authors.affiliation: Groupe Fonctionnel AEO (Adaptation Ecophysiologique et Ontogenèse), UMR 9190 MARBEC, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Rivera-Ingraham
authors.affiliation: Laboratorio de Fisiología (IHEM-CONICET), and Instituto de Fisiología (Facultad de Ciencias Médicas, Universidad Nacional de Cuyo), Casilla de Correo 33, 5500 Mendoza, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Giraud-Billoud
authors.affiliation: Laboratório de Radicais Livres, Departamento de Biologia Celular, Universidade de Brasília, Brasí;lia, DF, 70910-900, Brazil; Laboratório de Espectrometria de Massa, Embrapa Recursos Genéticos e Biotecnologia, Brasí;lia, DF, Brazil.
authors.forename: Thiago C
authors.initials: TC
authors.lastname: Genaro-Mattos
authors.affiliation: Laboratório de Radicais Livres, Departamento de Biologia Celular, Universidade de Brasília, Brasí;lia, DF, 70910-900, Brazil.
authors.forename: Élida G
authors.initials: ÉG
authors.lastname: Campos
mesh_terms: D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D053858:Metabolic Networks and Pathways; D018384:Oxidative Stress
keywords: Anoxia; Dehydration; Estivation; Freeze tolerance; Hypoxia tolerance; Ischemia