scholarly journals Mutual antagonism between hypoxia-inducible factors 1  and 2  regulates oxygen sensing and cardio-respiratory homeostasis

2013 ◽  
Vol 110 (19) ◽  
pp. E1788-E1796 ◽  
Author(s):  
G. Yuan ◽  
Y.-J. Peng ◽  
V. D. Reddy ◽  
V. V. Makarenko ◽  
J. Nanduri ◽  
...  
Blood ◽  
2021 ◽  
Author(s):  
Gregg L. Semenza

Hypoxia-inducible factors (HIF) were discovered as activators of erythropoietin gene transcription in response to reduced O2 availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcription activity, respectively. Mutations in genes encoding components of the oxygen sensing pathway cause familial erythrocytosis. Several small molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcome in these disorders.


2000 ◽  
Vol 203 (8) ◽  
pp. 1253-1263 ◽  
Author(s):  
R.H. Wenger

Oxygen is essential to the life of all aerobic organisms. Virtually every cell type is able to sense a limited oxygen supply (hypoxia) and specifically to induce a set of oxygen-regulated genes. This review summarizes current concepts of mammalian oxygen-sensing and signal-transduction pathways. Since the discovery of the hypoxia-inducible factors (HIFs), a great deal of progress has been made in our comprehension of how hypoxia induces the expression of oxygen-regulated genes. The alpha subunit of the heterodimeric transcription factors HIF-1, 2 and 3 is unstable under normoxia but is rapidly stabilized upon exposure to hypoxic conditions. Following heterodimerization with the constitutively expressed beta subunit, HIFs activate the transcription of an increasing number of genes involved in maintaining oxygen homeostasis at the cellular, local and systemic levels.


Evolution ◽  
2012 ◽  
Vol 67 (3) ◽  
pp. 873-882 ◽  
Author(s):  
Kalle T. Rytkönen ◽  
Arash Akbarzadeh ◽  
Hamed K. Miandare ◽  
Hiroyasu Kamei ◽  
Cunming Duan ◽  
...  

2009 ◽  
Vol 66 (22) ◽  
pp. 3539-3554 ◽  
Author(s):  
James D. Webb ◽  
Mathew L. Coleman ◽  
Christopher W. Pugh

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Bo Wu ◽  
Huajian Teng ◽  
Li Zhang ◽  
Hong Li ◽  
Jing Li ◽  
...  

Based on the discovery of endogenous H2S production, many in depth studies show this gasotransmitter with a variety of physiological and pathological functions. Three enzymes, cystathionineβ-synthase (CBS), cystathionineγ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST), are involved in enzymatic production of H2S. Emerging evidence has elucidated an important protective role of H2S in hypoxic conditions in many mammalian systems. However, the mechanisms by which H2S senses and responses to hypoxia are largely elusive. Hypoxia-inducible factors (HIFs) function as key regulators of oxygen sensing, activating target genes expression under hypoxia. Recent studies have shown that exogenous H2S regulates HIF action in different patterns. The activation of carotid bodies is a sensitive and prompt response to hypoxia, rapidly enhancing general O2supply. H2S has been identified as an excitatory mediator of hypoxic sensing in the carotid bodies. This paper presents a brief review of the roles of these two pathways which contribute to hypoxic sensing of H2S.


Physiology ◽  
2015 ◽  
Vol 30 (5) ◽  
pp. 340-348 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Gregg L. Semenza

The discovery of carotid bodies as sensory receptors for detecting arterial blood oxygen levels, and the identification and elucidation of the roles of hypoxia-inducible factors (HIFs) in oxygen homeostasis have propelled the field of oxygen biology. This review highlights the gas-messenger signaling mechanisms associated with oxygen sensing, as well as transcriptional and non-transcriptional mechanisms underlying the maintenance of oxygen homeostasis by HIFs and their relevance to physiology and pathology.


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