Control of HIF-1α Levels Potentially Promotes the Tissue Repair in Various Conditions Through Target Gene Expression

2021 ◽  
Vol 6 (1) ◽  
pp. 1266-1274
Author(s):  
Riyadh Firdaus ◽  
Ani Retno Prijanti
Keyword(s):  
Tissue Repair ◽  
Target Gene ◽  
Hypoxia Inducible Factor ◽  
The Body ◽  
Beta Subunits ◽  
Oxygen Balance ◽  
Hypoxia Inducible Factor 1 ◽  
Systemic Hypoxia ◽  
Adaptation Response ◽  
Tumor Growth And Metastasis

Hypoxia inducible factor-1 (HIF-1) is a transcription factor that plays an important role in maintaining oxygen balance at both the cellular and systemic levels, and is associated with various controls in the body. HIF-1 is a heterodimer of alpha and beta subunits. Alpha subunits are mostly dependent on oxygen levels in the body. In many cancers, excessive HIF-1α is thought to be involved in the promotion of tumor growth and metastasis. In addition, in the induction of systemic hypoxia, there is an increase of HIF-1α in the heart, brain, and even the kidneys as an adaptation response to hypoxia. Several studies regarding HIF-1a expression in traumatic brain injury, found that HIF-1a increased immediately after TBI, and decreased significantly after 24 hours. This can be used as a basis for further research on HIF-1a control as an effort to stop tissue damage or even help tissue repair.

Persisting mild hypothermia suppresses hypoxia-inducible factor-1α protein synthesis and hypoxia-inducible factor-1-mediated gene expression

2010 ◽  
Vol 298 (3) ◽  
pp. R661-R671 ◽  
Author(s):  
Tomoharu Tanaka ◽  
Takuhiko Wakamatsu ◽  
Hiroki Daijo ◽  
Seiko Oda ◽  
Shinichi Kai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Low Temperature ◽  
Hypoxia Inducible Factor ◽  
The Body ◽  
The Other ◽  
Adaptation To Hypoxia ◽  
Hypoxia Inducible Factor 1 ◽  
Other Hand

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28–32°C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1α protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O2 conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O2 atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1α neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

scholarly journals Cathepsin L, a Target of Hypoxia-Inducible Factor-1-α, Is Involved in Melanosome Degradation in Melanocytes

2021 ◽  
Vol 22 (16) ◽  
pp. 8596
Author(s):  
Ji Young Kim ◽  
Eun Jung Lee ◽  
Yuri Ahn ◽  
Sujin Park ◽  
Yu Jeong Bae ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Cathepsin L ◽  
Hypoxia Inducible Factor ◽  
Luciferase Reporter ◽  
Lysosomal Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Lysosomal Protease ◽  
Hypoxic Conditions ◽  
Novel Target

Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome–lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome–lysosome fusion.

Hypoxia‐inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia‐inducible factor‐1

2010 ◽  
Vol 24 (11) ◽  
pp. 4443-4458 ◽  
Author(s):  
Tina Gimm ◽  
Melanie Wiese ◽  
Barbara Teschemacher ◽  
Anke Deggerich ◽  
Johannes Schödel ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Target Gene ◽  
Hypoxia Inducible Factor ◽  
Specific Target ◽  
Hypoxia Inducible Factor 1 ◽  
Specific Target Gene ◽  
Inducible Protein ◽  
Lipid Droplet Protein

scholarly journals Oxygen – the forgotten nutrient

2017 ◽  
Vol 6 ◽  
Author(s):  
Paul Trayhurn
Keyword(s):  
Deep Sea ◽  
Lung Diseases ◽  
Molecular Level ◽  
Hypoxia Inducible Factor ◽  
The Body ◽  
The Other ◽  
Anaerobic Glycolysis ◽  
Hypoxia Inducible Factor 1 ◽  
Nutritional Science ◽  
Relative Deficiency

AbstractO2 is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O2 is not customarily regarded as a nutrient, this reflecting the route by which it enters the body – through the lungs or gills in vertebrates, rather than via the mouth and gastrointestinal tract. A relative deficiency of O2 occurs at high altitudes and during deep-sea diving, to which distinct adaptations occur. Deficiency is also evident in lung diseases such as emphysema. Without O2, mitochondrial respiration and oxidative phosphorylation cannot take place. At a molecular level, cells adapt to O2 deficiency by switching from oxidative metabolism to anaerobic glycolysis and there are changes in the expression of a multiplicity of genes, driven by hypoxia-sensitive transcription factors, particularly hypoxia-inducible factor-1. It is argued that O2 should be fully included within the remit of nutritional science alongside the other essential macronutrients.

scholarly journals The NADPH Oxidase Subunit NOX4 Is a New Target Gene of the Hypoxia-inducible Factor-1

2010 ◽  
Vol 21 (12) ◽  
pp. 2087-2096 ◽  
Author(s):  
Isabel Diebold ◽  
Andreas Petry ◽  
John Hess ◽  
Agnes Görlach
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Target Gene ◽  
Hypoxia Inducible Factor ◽  
Oxygen Species ◽  
Protein Levels ◽  
Hypoxia Inducible Factor 1 ◽  
Signaling Axis ◽  
Pulmonary Artery Smooth Muscle ◽  
Responsive Element

NADPH oxidases are important sources of reactive oxygen species (ROS), possibly contributing to various disorders associated with enhanced proliferation. NOX4 appears to be involved in vascular signaling and may contribute to the response to hypoxia. However, the exact mechanisms controlling NOX4 levels under hypoxia are not resolved. We found that hypoxia rapidly enhanced NOX4 mRNA and protein levels in pulmonary artery smooth-muscle cells (PASMCs) as well as in pulmonary vessels from mice exposed to hypoxia. This response was dependent on the hypoxia-inducible transcription factor HIF-1α because overexpression of HIF-1α increased NOX4 expression, whereas HIF-1α depletion prevented this response. Mutation of a putative hypoxia-responsive element in the NOX4 promoter abolished hypoxic and HIF-1α–induced activation of the NOX4 promoter. Chromatin immunoprecipitation confirmed HIF-1α binding to the NOX4 gene. Induction of NOX4 by HIF-1α contributed to maintain ROS levels after hypoxia and hypoxia-induced proliferation of PASMCs. These findings show that NOX4 is a new target gene of HIF-1α involved in the response to hypoxia. Together with our previous findings that NOX4 mediates HIF-1α induction under normoxia, these data suggest an important role of the signaling axis between NOX4 and HIF-1α in various cardiovascular disorders under hypoxic and also nonhypoxic conditions.

scholarly journals Myeloid cell leukemia-1 (Mc1-1) is a candidate target gene of hypoxia-inducible factor-1 (HIF-1) in the testis

2012 ◽  
Vol 10 (1) ◽  
pp. 104 ◽  
Author(s):  
Michael A Palladino ◽  
Anoop Shah ◽  
Rebecca Tyson ◽  
Jaclyn Horvath ◽  
Christine Dugan ◽  
...  
Keyword(s):  
Target Gene ◽  
Hypoxia Inducible Factor ◽  
Myeloid Cell ◽  
Cell Leukemia ◽  
Hypoxia Inducible Factor 1 ◽  
Candidate Target ◽  
Candidate Target Gene
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