Melatonin and the von Hippel–Lindau/HIF-1 oxygen sensing mechanism: A review

2016 ◽  
Vol 1865 (2) ◽  
pp. 176-183 ◽  
Author(s):  
Jerry Vriend ◽  
Russel J. Reiter
Keyword(s):  
Oxygen Sensing ◽  
Von Hippel Lindau ◽  
Sensing Mechanism

Analysis of von Hippel–Lindau Hereditary Cancer Syndrome: Implications of Oxygen Sensing

2004 ◽  
pp. 320-335 ◽  
Author(s):  
Haifeng Yang ◽  
Mircea Ivan ◽  
Jung-Hyun Min ◽  
William Y Kim ◽  
William G Kaelin
Keyword(s):  
Hereditary Cancer ◽  
Oxygen Sensing ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Von Hippel Lindau

scholarly journals Hypoxia and Oxygen-Sensing Signaling in Gene Regulation and Cancer Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8162
Author(s):  
Guang Yang ◽  
Rachel Shi ◽  
Qing Zhang
Keyword(s):  
Gene Regulation ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Oxygen Sensing ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylases ◽  
Von Hippel Lindau ◽  
Oxygen Homeostasis ◽  
Jmjc Domain ◽  
Encoding Protein

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. The key molecules of the hypoxia/oxygen-sensing signaling include the transcriptional regulator hypoxia-inducible factor (HIF) which widely controls oxygen responsive genes, the central members of the 2-oxoglutarate (2-OG)-dependent dioxygenases, such as prolyl hydroxylase (PHD or EglN), and an E3 ubiquitin ligase component for HIF degeneration called von Hippel–Lindau (encoding protein pVHL). In this review, we summarize the current knowledge about the canonical hypoxia signaling, HIF transcription factors, and pVHL. In addition, the role of 2-OG-dependent enzymes, such as DNA/RNA-modifying enzymes, JmjC domain-containing enzymes, and prolyl hydroxylases, in gene regulation of cancer progression, is specifically reviewed. We also discuss the therapeutic advancement of targeting hypoxia and oxygen sensing pathways in cancer.

Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia

1992 ◽  
Vol 263 (3) ◽  
pp. F474-F481 ◽  
Author(s):  
C. C. Tan ◽  
K. U. Eckardt ◽  
J. D. Firth ◽  
P. J. Ratcliffe
Keyword(s):  
Oxygen Sensing ◽  
Significant Proportion ◽  
Response Characteristic ◽  
Normobaric Hypoxia ◽  
Severe Hypoxia ◽  
Mrna Levels ◽  
Rnase Protection ◽  
Sensing Mechanism ◽  
Liver And Kidney

Erythropoietin (EPO) mRNA levels were measured by ribonuclease (RNase) protection in organs from unstimulated rats and from animals after normobaric hypoxia or hemorrhagic anemia. Both liver and kidney responded to stimulation with large increases in EPO mRNA, but the response characteristic to graded stimulation was different. The liver responded poorly to mild normobaric hypoxia, accounting for only 2 +/- 1% of total EPO mRNA at 11% O2, but hepatic EPO mRNA levels increased steeply with more severe hypoxia so that at 7.5% O2 the liver contributed to 33 +/- 7% of the total. After hemorrhagic anemia, the liver also responded more strongly to more severe stimulation, but at all points it accounted for a significant proportion of total EPO mRNA, contributing 18 +/- 6% after removal of 2.5 ml (hematocrit 37.2 +/- 1.3%), increasing to 37 +/- 14% after venesection of 10.5 ml (hematocrit 15.8 +/- 0.8%). Studies of EPO mRNA in other organs confirmed that EPO production outside the liver and kidney were quantitatively insignificant in stimulated animals. However, the hypoxia-induced increases in EPO mRNA in brain, testis, and spleen suggest the existence of an oxygen-sensing mechanism at other sites.

scholarly journals Mitochondrial complex II regulates a distinct oxygen sensing mechanism in monocytes

2017 ◽  
Vol 26 (7) ◽  
pp. 1328-1339 ◽  
Author(s):  
Shraddha Sharma ◽  
Jianming Wang ◽  
Eduardo Cortes Gomez ◽  
Robert T. Taggart ◽  
Bora E. Baysal
Keyword(s):  
Oxygen Sensing ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Sensing Mechanism

Erythrocytosis Caused by Mutations in the PHD2 and VHL Genes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3663-3663 ◽  
Author(s):  
Melanie J. Percy ◽  
Paul W. Furlow ◽  
Frank G.C. Jones ◽  
Terry R.J. Lappin ◽  
Frank S. Lee ◽  
...  
Keyword(s):  
Target Genes ◽  
Tertiary Structure ◽  
Oxygen Sensing ◽  
Protein A ◽  
Hypoxia Inducible Factor ◽  
Feedback Mechanism ◽  
Compound Heterozygous ◽  
Von Hippel Lindau ◽  
Negative Feedback Mechanism ◽  
Binding Groove

Abstract Human diseases have provided important insights into the function of fundamental physiological processes, and studying erythrocytosis has increased our understanding of the oxygen sensing pathway. In some cases this rare disorder arises specifically from dysregulation of the erythropoietin (Epo) axis. Epo gene transcription is under the control of a negative feedback mechanism involving the kidneys, which sense tissue hypoxia at the molecular level via the hypoxia inducible factor (HIF) transcription complex. Both subunits of the HIF complex, alpha and beta, are constitutively expressed but only the beta subunit is detectable in the presence of oxygen. Key prolines in the oxygen degradation domain of HIFalpha are hydroxylated by a family of prolyl hydroxylase enzymes, PHD1-3. Of these PHD2 has the most widespread tissue distribution. Upon hydroxylation of HIF, the von Hippel Lindau (VHL) protein, a component of an E3 ligase complex, promotes the ubiquitination of the alpha subunit. HIFalpha is then targeted to the proteasome and the transcription of HIF target genes is prevented. In hypoxia the activity of the PHD enzymes is low and the HIF complex assembles causing upregulation of genes such as Epo. Over the last ten years we have maintained a registry of individuals with erythrocytosis. To date 181 patients have been included with clinical details and consented DNA samples have been collected. There is a preponderance of males with ratio of 1.7 males to each female. The mean age of erythrocytosis individuals on the registry is 37 years. The majority of erythrocytosis patients have inappropriately normal (46%) or raised (26%) serum Epo levels as compared to PV, where the Epo level is often undetectable. Thus it can be inferred that dysregulation of the Epo axis via the oxygen sensing pathway would be a significant cause of erythrocytosis. Consequently, PHD2 and VHL have been investigated. We have now identified 2 different mutations, Pro317Arg and Arg371His, in PHD2. In the tertiary structure of PHD2, Pro317and Arg371 are close to essential iron binding residues and furthermore suggest the location of a HIF binding groove. The Arg200Trp VHL mutation, commonly described as the Chuvash mutation, has been detected in 8 Asian families and their large kindred. Two Western European individuals were found to be compound heterozygous for the Arg200Trp and either the novel Pro192Thr or Gly144Arg variants. Intriguingly 2 further individuals possess one wild type and one mutated allele, Arg200Trp or Leu188Val. Screening other genes of the oxygen sensing pathway has failed to reveal further defects in these individuals. In summary, defects in the oxygen sensing pathway are associated with the development of erythrocytosis. Mutations in VHL are more common than PHD2 and highlight the importance of these proteins in the maintenance of red cell homeostasis.

The oxygen sensing mechanism of a triphenylamine-based cyclometalated platinum(II) complex

2019 ◽  
Vol 208 ◽  
pp. 46-50
Author(s):  
Yu Ning ◽  
Xuedan Song ◽  
Heming Zhang ◽  
Tianqing Liu ◽  
Ce Hao
Keyword(s):  
Oxygen Sensing ◽  
Sensing Mechanism
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