scholarly journals The redox-sensitive human antioxidant responsive element induces gene expression under low oxygen conditions

1998 ◽  
Vol 19 (8) ◽  
pp. 1333-1337 ◽  
Author(s):  
N. Waleh
2008 ◽  
Vol 190 (23) ◽  
pp. 7864-7867 ◽  
Author(s):  
James Niemann ◽  
Louis S. Tisa

ABSTRACT The Frankia genome contains two truncated hemoglobin genes (hboN and hboO) whose functions remain to be determined. Nitric oxide (NO) generated by the addition of 400 μM SNAP (S-nitroso-N-acetylpenicillamine) caused a 10-fold increase in hboN gene expression but had no effect on hboO expression. The addition of the NO scavenger, carboxy-PT10, reduced the effect of SNAP. hboO gene expression increased under low-oxygen conditions, while hboN expression was unaffected. These results suggest that HboN may function in protection from nitrosative stress and that HboO may act as an oxygen transport molecule for increased respiration in hypoxic environments.


2005 ◽  
Vol 390 (1) ◽  
pp. 189-197 ◽  
Author(s):  
Nuria Pescador ◽  
Yolanda Cuevas ◽  
Salvador Naranjo ◽  
Marisa Alcaide ◽  
Diego Villar ◽  
...  

Low oxygen levels induce an adaptive response in cells through the activation of HIFs (hypoxia-inducible factors). These transcription factors are mainly regulated by a group of proline hydroxylases that, in the presence of oxygen, target HIF for degradation. The expression of two such enzymes, EGLN1 [EGL nine homologous protein 1, where EGL stands for egg laying defective (Caenorhabditis elegans gene)] and EGLN3, is induced by hypoxia through a negative feedback loop, and we have demonstrated recently that hypoxic induction of EGLN expression is HIF-dependent. In the present study, we have identified an HRE (hypoxia response element) in the region of the EGLN3 gene using a combination of bioinformatics and biological approaches. Initially, we isolated a number of HRE consensus sequences in a region of 40 kb around the human EGLN3 gene and studied their evolutionary conservation. Subsequently, we examined the functionality of the conserved HRE sequences in reporter and chromatin precipitation assays. One of the HREs, located within a conserved region of the first intron of the EGLN3 gene 12 kb downstream of the transcription initiation site, bound HIF in vivo. Furthermore, this sequence was able to drive reporter gene expression under conditions of hypoxia in an HRE-dependent manner. Indeed, we were able to demonstrate that HIF was necessary and sufficient to induce gene expression from this enhancer sequence.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44621 ◽  
Author(s):  
Eva E. R. Philipp ◽  
Wiebke Wessels ◽  
Heike Gruber ◽  
Julia Strahl ◽  
Anika E. Wagner ◽  
...  

2004 ◽  
Vol 183 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Masami Hayashi ◽  
Masahiro Sakata ◽  
Takashi Takeda ◽  
Toshiya Yamamoto ◽  
Yoko Okamoto ◽  
...  

Glucose transporter 1 (GLUT1) plays an important role in the transport of glucose in the placenta. During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development, and GLUT1 expression is enhanced in response to oxygen deficiency in the placenta. Hypoxia-inducible factor-1 (HIF-1)α is involved in the induction of GLUT1 expression in other cells. The present study was designed to test whether HIF-1α is involved in hypoxia-induced activation of GLUT1 expression using trophoblast-derived human BeWo and rat Rcho-1 cells as models. GLUT1 mRNA and protein expression were elevated under 5% O2 or in the presense of cobalt chloride, which has been shown to mimic hypoxia. Using rat GLUT1 (rGLUT1) promoter–luciferase constructs, we showed that this up-regulation was mediated at the transcriptional level. Deletion mutant analysis of the rGLUT1 promoter indicated that a 184 bp hypoxia-responsive element (HRE) of the promoter was essential to increase GLUT1 reporter gene expression in response to low-oxygen conditions. BeWo and Rcho-1 cells cultured under 5% O2 or with CoCl2 showed increased expression of HIF-1α protein compared with those cultured under 20% O2. To test whether this factor is directly involved in hypoxia-induced GLUT1 promoter activation, BeWo and Rcho-1 cells were transiently transfected with an HIF-1α expression vector. Exogeneous HIF-1α markedly increased the GLUT1 promoter activity from constructs containing the HRE site, while the GLUT1 promoter constructs lacking the HRE site were not activated by exogenous HIF-1α These data demonstrate that GLUT1 is up-regulated under 5% O2 or in the presence of CoCl2 in the placental cell lines through HIF-1α interaction with a consensus HRE site of the GLUT1 promoter.


2018 ◽  
Author(s):  
Masahiro Yasunaga ◽  
Shinji Saijou ◽  
Shingo Hanaoka ◽  
Takahiro Anzai ◽  
Ryo Tsumura ◽  
...  

AbstractThe present state of therapy for colorectal cancer (CRC) is far from satisfactory, highlighting the need for new targets for this disease. We identified a new colorectal cancer (CRC)-specific molecule, TMEM180, a predicted eleven-pass transmembrane protein that apparently functions as a cation symporter. Our anti-TMEM180 monoclonal antibody (mAb) eradicated SW480 CRC xenografts in mice. The TMEM180 promoter region contains ten hypoxia-responsive element consensus sequences; accordingly SW480 cells upregulated TMEM180 under low-oxygen conditions. TMEM180 expression in SW480 cells was positively correlated with anchorage-independent colony formation and tumourigenesis. TMEM180-positive SW480 cells resided at the tumour–stroma interface manifested by αSMA-positive fibroblasts, also known as the tumour niche. Some clusters of TMEM180-positive cells adjacent to the niche were integrin α6-positive. These data indicate that TMEM180 represents a possible cancer stem cell marker and that a mAb against this protein could be used as antibody-based therapeutic against CRC.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jungwon Choi ◽  
Wontae Kim ◽  
Hyejin Yoon ◽  
Jaewang Lee ◽  
Jin Hyun Jun

Oxygen tension is one of the most critical factors for mammalian embryo development and its survival. The HIF protein is an essential transcription factor that activated under hypoxic conditions. In this study, we evaluated the effect of dynamic oxygen conditions on the expression of embryonic genes and translocation of hypoxia-inducible factor-1α (HIF-1α) in cultured mouse blastocysts. Two-pronuclear (2PN) zygotes harvested from ICR mice were subjected to either high oxygen (HO; 20%), low oxygen (LO; 5%), or dynamic oxygen (DO; 5% to 2%) conditions. In the DO group, PN zygotes were cultured in 5% O2 from days 1 to 3 and then in 2% O2 till day 5 after hCG injection. On day 5, the percentage of blastocysts in the cultured embryos from each group was estimated, and the embryos were also subjected to immunocytochemical and gene expression analysis. We found that the percentage of blastocysts was similar among the experimental groups; however, the percentage of hatching blastocysts in the DO and LO groups was significantly higher than that in the HO group. The total cell number of blastocysts in the DO group was significantly higher than that of both the HO and LO groups. Further, gene expression analysis revealed that the expression of genes related to the embryonic development was significantly higher in the DO group than that in the HO and LO groups. Interestingly, HIF-1α mRNA expression did not significantly differ; however, HIF-1α protein translocation from the cytoplasm to the nucleus was significantly higher in the DO group than in the HO and LO groups. Our study suggests that dynamic oxygen concentrations increase the developmental capacity in mouse preimplantation embryos through activation of the potent transcription factor HIF-1α.


2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.


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