Faculty Opinions recommendation of Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2).

2006 ◽  
Author(s):  
Michael Maroney
Keyword(s):  
Crystal Structure ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Cellular Oxygen

scholarly journals Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)

2006 ◽  
Vol 103 (26) ◽  
pp. 9814-9819 ◽  
Author(s):  
M. A. McDonough ◽  
V. Li ◽  
E. Flashman ◽  
R. Chowdhury ◽  
C. Mohr ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Cellular Oxygen

scholarly journals Nitric Oxide Modulates Oxygen Sensing by Hypoxia-inducible Factor 1-dependent Induction of Prolyl Hydroxylase 2

2006 ◽  
Vol 282 (3) ◽  
pp. 1788-1796 ◽  
Author(s):  
Utta Berchner-Pfannschmidt ◽  
Hatice Yamac ◽  
Buena Trinidad ◽  
Joachim Fandrey
Keyword(s):  
Nitric Oxide ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Hypoxia Inducible Factor 1

scholarly journals Intermittent hypoxia enhances the expression of HIF1A by increasing the quantity and catalytic activity of KDM4A-C and demethylating H3K9me3 at the HIF1A locus

2021 ◽  
Author(s):  
Chloe-Anne Martinez ◽  
Neha Bal ◽  
Peter A Cistulli ◽  
Kristina M Cook
Keyword(s):  
Intermittent Hypoxia ◽  
Target Genes ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Sensing Systems ◽  
Cellular Oxygen ◽  
Fine Tune

Cellular oxygen-sensing pathways are primarily regulated by hypoxia inducible factor-1 (HIF-1) in chronic hypoxia and are well studied. Intermittent hypoxia also occurs in many pathological conditions, yet little is known about its biological effects. In this study, we investigated how two proposed cellular oxygen sensing systems, HIF-1 and KDM4A-C, respond to cells exposed to intermittent hypoxia and compared to chronic hypoxia. We found that intermittent hypoxia increases HIF-1 activity through a pathway distinct from chronic hypoxia, involving the KDM4A, -B and -C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A-C resulting in a decrease in H3K9 methylation. This contrasts with chronic hypoxia, which decreases KDM4A-C activity, leading to hypermethylation of H3K9. Demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia.

Mitochondria and cellular oxygen sensing in the HIF pathway

2007 ◽  
Vol 409 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Cormac T. Taylor
Keyword(s):  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Oxygen Demand ◽  
Molecular Response ◽  
Diverse Range ◽  
Cellular Processes ◽  
Disease States ◽  
Final Electron ◽  
Cellular Oxygen ◽  
Hif Pathway

Mitochondrial respiration is responsible for more than 90% of oxygen consumption in humans. Cells utilize oxygen as the final electron acceptor in the aerobic metabolism of glucose to generate ATP which fuels most active cellular processes. Consequently, a drop in tissue oxygen levels to the point where oxygen demand exceeds supply (termed hypoxia) leads rapidly to metabolic crisis and represents a severe threat to ongoing physiological function and ultimately, viability. Because of the central role of oxygen in metabolism, it is perhaps not surprising that we have evolved an efficient and rapid molecular response system which senses hypoxia in cells, leading to the induction of an array of adaptive genes which facilitate increased oxygen supply and support anaerobic ATP generation. This response is governed by HIF (hypoxia-inducible factor). The oxygen sensitivity of this pathway is conferred by a family of hydroxylases which repress HIF activity in normoxia allowing its rapid activation in hypoxia. Because of its importance in a diverse range of disease states, the mechanism by which cells sense hypoxia and transduce a signal to the HIF pathway is an area of intense investigation. Inhibition of mitochondrial function reverses hypoxia-induced HIF leading to speculation of a role for mitochondria in cellular oxygen sensing. However, the nature of the signal between mitochondria and oxygen-sensing hydroxylase enzymes has remained controversial. In the present review, two models of the role for mitochondria in oxygen sensing will be discussed and recent evidence will be presented which raises the possibility that these two models which implicate ROS (reactive oxygen species) and oxygen redistribution respectively may complement each other and facilitate rapid and dynamic activation of the HIF pathway in hypoxia.

Oxygen-sensing mechanisms in development and tissue repair

Development ◽  
2021 ◽  
Vol 148 (23) ◽  
Author(s):  
Yida Jiang ◽  
Li-Juan Duan ◽  
Guo-Hua Fong
Keyword(s):  
Clinical Relevance ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Loss Of Function ◽  
Mouse Development ◽  
Α Subunits ◽  
Prolyl Hydroxylase Domain

ABSTRACT Under normoxia, hypoxia inducible factor (HIF) α subunits are hydroxylated by PHDs (prolyl hydroxylase domain proteins) and subsequently undergo polyubiquitylation and degradation. Normal embryogenesis occurs under hypoxia, which suppresses PHD activities and allows HIFα to stabilize and regulate development. In this Primer, we explain molecular mechanisms of the oxygen-sensing pathway, summarize HIF-regulated downstream events, discuss loss-of-function phenotypes primarily in mouse development, and highlight clinical relevance to angiogenesis and tissue repair.

Ancient Atmospheres and the Evolution of Oxygen Sensing Via the Hypoxia-Inducible Factor in Metazoans

Physiology ◽  
2010 ◽  
Vol 25 (5) ◽  
pp. 272-279 ◽  
Author(s):  
Cormac T. Taylor ◽  
Jennifer C. McElwain
Keyword(s):  
Oxygen Sensing ◽  
Atmospheric Oxygen ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Oxygen Levels ◽  
Selection Force ◽  
Cellular Oxygen ◽  
Hif Pathway ◽  
Evolution Of Oxygen ◽  
Oxygen Concentrations

Metazoan diversification occurred during a time when atmospheric oxygen levels fluctuated between 15 and 30%. The hypoxia-inducible factor (HIF) is a primary regulator of the adaptive transcriptional response to hypoxia. Although the HIF pathway is highly conserved, its complexity increased during periods when atmospheric oxygen concentrations were increasing. Thus atmospheric oxygen levels may have provided a selection force on the development of cellular oxygen-sensing pathways.

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