Hypoxia-Inducible Factor 1 (HIF-1) Mediated Adaptive Responses in the Solid Tumor

2010 ◽  
pp. 271-290
Author(s):  
Tereza Goliasova ◽  
Nicholas C. Denko
Keyword(s):  
Solid Tumor ◽  
Hypoxia Inducible Factor ◽  
Adaptive Responses ◽  
Hypoxia Inducible Factor 1

scholarly journals Accelerated tumor growth under intermittent hypoxia is associated with hypoxia-inducible factor-1-dependent adaptive responses to hypoxia

Oncotarget ◽  
2017 ◽  
Vol 8 (37) ◽  
pp. 61592-61603 ◽  
Author(s):  
Dae Wui Yoon ◽  
Daeho So ◽  
Sra Min ◽  
Jiyoung Kim ◽  
Mingyu Lee ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Intermittent Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Adaptive Responses ◽  
Hypoxia Inducible Factor 1

Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1

Physiology ◽  
2009 ◽  
Vol 24 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Gregg L. Semenza
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Intermittent Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Systemic Hypertension ◽  
Adaptive Responses ◽  
Hypoxia Inducible Factor 1 ◽  
Oxygen Homeostasis ◽  
Genes Encoding

Metazoan organisms are dependent on a continuous supply of O2 for survival. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in development, physiology, and disease. HIF-1 activity is induced in response to continuous hypoxia, intermittent hypoxia, growth factor stimulation, and Ca2+ signaling. HIF-1 mediates adaptive responses to hypoxia, including erythropoiesis, angiogenesis, and metabolic reprogramming. In each case, HIF-1 regulates the expression of multiple genes encoding key components of the response pathway. HIF-1 also mediates maladaptive responses to chronic continuous and intermittent hypoxia, which underlie the development of pulmonary and systemic hypertension, respectively.

scholarly journals Hypoxia inducible factor-1 alpha (Hif-1 alpha) polymorphism in lymphoma and reactive lymphoid hyperplasia

2019 ◽  
Vol 4 (2) ◽  
pp. 35-40
Author(s):  
SEMA YILMAZ ◽  
Asim Yoruk ◽  
Itır Ebru Zemheri ◽  
Aysegul Kuskucu ◽  
Oznur Suakar ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Gene Polymorphisms ◽  
Early Stage ◽  
Hypoxia Inducible Factor ◽  
Lymphoid Hyperplasia ◽  
Reactive Lymphoid Hyperplasia ◽  
Adaptive Responses ◽  
Cancer Etiology ◽  
Hypoxia Inducible Factor 1 ◽  
Meaningful Relationship

Background: Lymphadenopathy is an abnormality in the size or the character of the lymph node.  It may be a manifestation of infectious and malignant diseases. Reactive lymphoid hyperplasia is a benign form of lymphadenopathy. Cells develop numerous adaptive responses regulated by hypoxia inducible factor-1 alpha (Hif-1 alpha) against hypoxic stress. Purpose: Hif-1alpha may play a role in the process of carcinogenesis in the early stage of cancer. We aimed to investigate the most common polymorphism of Hif-1α  C1772T and G1790A gene polymorphisms in reactive lymphoid hyperplasia and lymphoma cases. Methods: Eighty-six paraffin-embedded blocs [51 (59,3%) reactive lymphoid hyperplasia; (40,7%) lymphoma] were examined. DNA was extracted from these samples and the polymerase chain reaction (PCR) was carried out. After DNA isolation, Hif-1α C1772T and G1790A polymorphisms were investigated with pyrosequencing. Results: Cases were  (29,1%) girls and 61 (70,9%) boys. The mean age was 91,47±57,96 and 142,46±41,66 for reactive lymphoid hyperplasia and lymphoma group, respectively. There was no Hif-1α C1772T gene polymorphism in both group, but Hif-1α G1790A gene polymorphism was recorded in 14 cases (reactive lymphoid hyperplasia 10, lymphoma 4). Although Hif-1α G1790A gene polymorphism was seen a little higher in reactive lymphoid hyperplasia cases than that of lymphoma, no meaningful relationship was found statistically between two groups (p>0,05). Conclusion: Hif-1α C1772T and G1790A gene polymorphisms had been interrogated in cancer etiology and emphasized in some cancers. In our study, considering of a few of Hif-1α G1790A gene polymorphism in reactive lymphoid hyperplasia group, it should be investigated with large studies in terms of understanding of the behavior of Hif- 1α gene polymorphisms in children with lymphadenopathy.

scholarly journals Inhibition of hypoxia-inducible factor 1α accumulation by glyceryl trinitrate and cyclic guanosine monophosphate

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Judy Kim ◽  
Ivraym B. Barsoum ◽  
Harrison Loh ◽  
Jean-François Paré ◽  
D. Robert Siemens ◽  
...  
Keyword(s):  
Glyceryl Trinitrate ◽  
Hypoxia Inducible Factor ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Protein Accumulation ◽  
Dependent Manner ◽  
Adaptive Responses ◽  
Calpain Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Cgmp Signalling

Abstract A key mechanism mediating cellular adaptive responses to hypoxia involves the activity of hypoxia-inducible factor 1 (HIF-1), a transcription factor composed of HIF-1α, and HIF-1β subunits. The classical mechanism of regulation of HIF-1 activity involves destabilisation of HIF-1α via oxygen-dependent hydroxylation of proline residues and subsequent proteasomal degradation. Studies from our laboratory revealed that nitric oxide (NO)-mediated activation of cyclic guanosine monophosphate (cGMP) signalling inhibits the acquisition of hypoxia-induced malignant phenotypes in tumour cells. The present study aimed to elucidate a mechanism of HIF-1 regulation involving NO/cGMP signalling. Using human DU145 prostate cancer cells, we assessed the effect of the NO mimetic glyceryl trinitrate (GTN) and the cGMP analogue 8-Bromo-cGMP on hypoxic accumulation of HIF-1α. Concentrations of GTN known to primarily activate the NO/cGMP pathway (100 nM–1 µM) inhibited hypoxia-induced HIF-1α protein accumulation in a time-dependent manner. Incubation with 8-Bromo-cGMP (1 nM–10 µM) also attenuated HIF-1α accumulation, while levels of HIF-1α mRNA remained unaltered by exposure to GTN or 8-Bromo-cGMP. Furthermore, treatment of cells with the calpain (Ca2+-activated proteinase) inhibitor calpastatin attenuated the effects of GTN and 8-Bromo-cGMP on HIF-1α accumulation. However, since calpain activity was not affected by incubation of DU145 cells with various concentrations of GTN or 8-Bromo-cGMP (10 nM or 1 µM) under hypoxic or well-oxygenated conditions, it is unlikely that NO/cGMP signalling inhibits HIF-1α accumulation via regulation of calpain activity. These findings provide evidence for a role of NO/cGMP signalling in the regulation of HIF-1α, and hence HIF-1-mediated hypoxic responses, via a mechanism dependent on calpain.

scholarly journals HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance

2019 ◽  
Vol 20 (2) ◽  
pp. 238 ◽  
Author(s):  
Ayako Nagao ◽  
Minoru Kobayashi ◽  
Sho Koyasu ◽  
Christalle C. T. Chow ◽  
Hiroshi Harada
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathway ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Hypoxia Inducible Factor ◽  
Pentose Phosphate ◽  
Adaptive Responses ◽  
Acid Fermentation ◽  
Hypoxia Inducible Factor 1 ◽  
The Warburg Effect

Normal cells produce adenosine 5′-triphosphate (ATP) mainly through mitochondrial oxidative phosphorylation (OXPHOS) when oxygen is available. Most cancer cells, on the other hand, are known to produce energy predominantly through accelerated glycolysis, followed by lactic acid fermentation even under normoxic conditions. This metabolic phenomenon, known as aerobic glycolysis or the Warburg effect, is less efficient compared with OXPHOS, from the viewpoint of the amount of ATP produced from one molecule of glucose. However, it and its accompanying pathway, the pentose phosphate pathway (PPP), have been reported to provide advantages for cancer cells by producing various metabolites essential for proliferation, malignant progression, and chemo/radioresistance. Here, focusing on a master transcriptional regulator of adaptive responses to hypoxia, the hypoxia-inducible factor 1 (HIF-1), we review the accumulated knowledge on the molecular basis and functions of the Warburg effect and its accompanying pathways. In addition, we summarize our own findings revealing that a novel HIF-1-activating factor enhances the antioxidant capacity and resultant radioresistance of cancer cells though reprogramming of the glucose metabolic pathway.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

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