Abstract：
:Although once considered by biologists almost exclusively for their toxicity, reactive oxygen (ROS) and nitrogen (RNS) species produced within normal cells under baseline physiological conditions are now appreciated as redox regulators of a wide range of protein functions. Two families of enzymes, the NADPH oxidases (NOXs) and nitric oxide synthases (NOSs), are major sources of ROS/RNS from molecular oxygen. Aquaporins (AQPs) are membrane channels capable of transporting some ROS/RNS, in particular hydrogen peroxide and perhaps nitric oxide. The activities of all these enzymes and channels are sensitive to variations in oxygen levels within the physiological range experienced by cells in the human body. Since ROS/RNS have important physiological roles and their endogenous production is affected by oxygen levels, we hypothesize that the synthesis of these proteins is increased at lower oxygen levels within the physiological range of most human cells in vivo, i.e. 2-5%, in order to facilitate the maintenance of ROS/RNS production rates. We further postulate that this is achieved, at least in part, by transcriptional stimulation mediated by the activity of hypoxia inducible factors (HIFs), which are strongly regulated by oxygen levels over the same range of oxygen. Here we survey the evidence supporting this hypothesis, including induction of expression of NOXs, NOSs, and AQPs at lower oxygen levels, presence of hypoxia response elements in the corresponding human genes, and evidence from chromatin immunoprecipitation (ChIP) experiments that HIF-1 and/or HIF-2 bind these regions. We find a significant amount of empirical data supporting the hypothesis that HIFs could function as physiological regulators of ROS/RNS homeostasis in the normoxic range in human cells.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Stuart JA,Aibueku O,Bagshaw O,Moradi Fdoi
10.1016/j.mehy.2019.109249subject
Has Abstractpub_date
2019-08-01 00:00:00pages
109249eissn
0306-9877issn
1532-2777pii
S0306-9877(19)30041-6journal_volume
129pub_type
杂志文章abstract：:The ability of tumor cells to differentiate in combination with their ability to express genes that are not expressed in normal tissues, may result in the emergence of new cell types in evolution. Tumors may play an evolutionary role by providing conditions (space and resources) for the expression of newly evolving ge...
journal_title：Medical hypotheses
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2009-11-01 00:00:00
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更新日期：2013-10-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Medical hypotheses
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更新日期：2008-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2009-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
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更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2008-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
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更新日期：2010-04-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(79)90079-3
更新日期：1979-08-01 00:00:00
