Premium
Cellular and molecular mechanisms in the hypoxic tissue: role of HIF‐1 and ROS
Author(s) -
Zepeda Andrea B.,
Pessoa Adalberto,
Castillo Rodrigo L.,
Figueroa Carolina A.,
Pulgar Victor M.,
Farías Jorge G.
Publication year - 2013
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.2985
Subject(s) - reactive oxygen species , microbiology and biotechnology , transcription factor , mediator , oxidative phosphorylation , hypoxia (environmental) , intracellular , biology , signal transduction , superoxide , adenosine triphosphate , chemistry , biochemistry , oxygen , gene , enzyme , organic chemistry
Reactive oxygen species such as superoxide anion radicals (O 2 − ) and hydrogen peroxide (H 2 O 2 ) have for long time been recognized as undesirable by‐products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast‐acting mechanisms acting within a wide range of partial pressures of oxygen (O 2 ). Intracellular O 2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia‐inducible factor 1 (HIF‐1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O 2 ‐dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF‐1 coordinately regulates tissue O 2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro‐oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF‐mediated O 2 sensing mechanisms and their interactions with reactive oxygen species–generating pathways in normal and abnormal physiology. Copyright © 2013 John Wiley & Sons, Ltd.