scholarly journals Role of HIF-1, Siah-1 and SKN-1 in Inducing Adiposity for Caenorhabditis elegans under Hypoxic Conditions

2020 ◽  
Vol 12 (1) ◽  
pp. 51-6
Author(s):  
I Gede Widhiantara ◽  
Anak Agung Ayu Putri Permatasari ◽  
I Wayan Rosiana ◽  
I Wayan Putu Sutirtayasa ◽  
Ferbian Milas Siswanto
Keyword(s):  
Body Length ◽  
Hypoxia Inducible Factors ◽  
Fat Accumulation ◽  
C Elegans ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Upstream Regulator ◽  
Morphometry Analysis ◽  
Seven In Absentia

BACKGROUND: Hypoxia has been shown to be able to induce adiposity. However, the mechanism and factors involved in this effect still remains unclear. Hence, we sought to investigate the role of oxygensensitive factors regarding hypoxia-induced adiposity in nematode Caenorhabditis elegans.METHODS: The C. elegans were grown on nematode growth medium (NGM) agar plates seeded with Escherichia coli OP50 at 20°C. The ratio of width/body length was measured using the morphometry analysis. Fat accumulation was examined using Sudan Black methods. Protein levels of sterol binding protein (SBP)-1 were assessed by immunoblotting. Lifespan assay was performed at 20°C and was monitored every two days.RESULTS: The results showed that of all mutant used, only hif-1 mutant which did not experience an increase in the ratio of width/body length (p>0.05) and fat accumulation (p>0.05), indicating that hypoxia-inducible factors (HIF)-1 plays an important role in the pathogenesis of hypoxia-induced adiposity. Both siah-1 and skn-1 mutants experienced SBP-1 protein elevation (p<0.05), and increased fat-6 mRNA expression (p<0.05) which were not experienced by a hif-1 mutant (p>0.05) further supporting that HIF-1 acts as an upstream regulator fromSBP-1.CONCLUSION: In general, the results of this study provide evidences of the involvement of the transcription factor HIF-1 in inducing adiposity under the hypoxic conditions. However, we did not find the involvement of seven in absentia homolog-1 (Siah-1) and skinhead-1 (SKN-1).KEYWORDS: hypoxia, adiposity, fat, HIF-1, Siah-1, SKN-1, C. elegans

scholarly journals Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

2020 ◽  
Author(s):  
Yijing Chu ◽  
Chongyu Yue ◽  
Wei Peng ◽  
Weiping Chen ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chorionic Villus ◽  
Pcr Analysis ◽  
Rna Seq ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Upstream Regulator ◽  
Pathway Analyses ◽  
Stat3 Signalling

Abstract Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function.Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts.Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment.Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

scholarly journals Zeaxanthin Inhibits Hypoxia-Induced VEGF Secretion by RPE Cells through Decreased Protein Levels of Hypoxia-Inducible Factors-1α

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Richard Rosen ◽  
Tommaso Vagaggini ◽  
Yueqin Chen ◽  
Dan-Ning Hu
Keyword(s):  
Culture Medium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Hypoxia Inducible Factors ◽  
Rpe Cells ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Cell Hypoxia ◽  
Important Stimulus

Hypoxia is the most important stimulus leading to upregulation of VEGF in the retina and this is caused by accumulation of hypoxia-inducible factors-1α(HIF-1α) protein. The effects of zeaxanthin, a natural phytochemical, on the VEGF and HIF-1αexpression in the primary culture of human retinal pigment epithelial (RPE) cells were studied. An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without zeaxanthin under normoxic and hypoxic conditions. VEGF and HIF-1αprotein and RNA levels were measured by ELISA kits and RT-PCR, respectively. Hypoxia caused a significant increase of VEGF expression and accumulation of HIF-1αin RPE cells. Zeaxanthin at 50–150 μM significantly inhibited the expression of VEGF and accumulation of HIF-1αprotein caused by hypoxia but did not affect expression of VEGF and HIF-1αunder normoxic conditions. This is the first report on the effect of zeaxanthin on VEGF and HIF-1αlevels in cultured RPE cells and suggests that zeaxanthin may have potential value in the prevention and treatment of various retinal diseases associated with vascular leakage and neovascularization.

scholarly journals Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yijing Chu ◽  
Chengzhan Zhu ◽  
Chongyu Yue ◽  
Wei Peng ◽  
Weiping Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chorionic Villus ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Upstream Regulator ◽  
Before And After ◽  
Pathway Analyses ◽  
Stat3 Signalling ◽  
Proliferation And Invasion

Abstract Background Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. Several studies have revealed that human chorionic villous mesenchymal stem cells (CV-MSCs) could regulate trophoblasts function. Results To understand how human chorionic villous mesenchymal stem cells (CV-MSCs) regulate trophoblast function, we treated trophoblasts with CV-MSC supernatant under hypoxic conditions. Treatment markedly enhanced proliferation and invasion and augmented autophagy. Transcriptome and pathway analyses of trophoblasts before and after treatment revealed JAK2/STAT3 signalling as an upstream regulator. In addition, STAT3 mRNA and protein levels increased during CV-MSC treatment. Consistent with these findings, JAK2/STAT3 signalling inhibition reduced the autophagy, survival and invasion of trophoblasts, even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, STAT3 overexpression increased autophagy levels in trophoblasts; thus, it positively regulated autophagy in hypoxic trophoblasts. Human placental explants also proved our findings by showing that STAT3 was activated and that LC3B-II levels were increased by CV-MSC treatment. Conclusion In summary, our data suggest that CV-MSC-dependent JAK2/STAT3 signalling activation is a prerequisite for autophagy upregulation in trophoblasts. Graphic abstract

scholarly journals Hypoxic Proliferation of Osteosarcoma Cells Depends on Arginase II

2016 ◽  
Vol 39 (2) ◽  
pp. 802-813 ◽  
Author(s):  
Bhuvana A. Setty ◽  
Yi Jin ◽  
Peter J. Houghton ◽  
Nicholas D. Yeager ◽  
Thomas G. Gross ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Osteosarcoma Cells ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Human Osteosarcoma Cell ◽  
Arginase Ii

Background/Aims: Despite significant advancements in the diagnosis and treatment of osteosarcoma, the overall survival has remained relatively unchanged for over two decades. Hypoxic conditions have been demonstrated in solid tumors and are associated with increased cell proliferation and angiogenesis. L-arginine metabolism by arginase produces L-ornithine, the precursor for polyamine and proline synthesis required for cellular proliferation. We hypothesized that hypoxia would increase cellular proliferation via arginase induction in human osteosarcoma cell lines. Methods: We utilized a variety of approaches to examine the role of arginase II in hypoxic (1% O2, 5% CO2) cellular proliferation. Results: Arginase II mRNA and protein levels were significantly increased in osteosarcoma cells exposed to hypoxia for 48 hours. There were twice as many viable cells following 48 hours of hypoxia than following 48 hours of normoxia (21% O2, 5% CO2). The addition of difluoromethylornithine (DFMO), a putative arginase inhibitor, prevented hypoxia-induced proliferation. Transfection of small interfering RNAs (siRNA) targeting arginase II resulted in knockdown of arginase II protein levels and prevented hypoxia-induced cellular proliferation. Conclusions: These data support our hypothesis that hypoxia increases proliferation of osteosarcoma cells in an arginase II-dependent manner. We speculate that arginase II may represent a therapeutic target in osteosarcoma.

scholarly journals Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

2020 ◽  
Author(s):  
Yijing Chu ◽  
Chongyu Yue ◽  
Wei Peng ◽  
Weiping Chen ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chorionic Villus ◽  
Pcr Analysis ◽  
Rna Seq ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Upstream Regulator ◽  
Pathway Analyses ◽  
Stat3 Signalling

Abstract Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function. Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts. Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment. Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

304. Murine HIF-1α localisation by immunohistochemistry in a mouse reproductive tissue

2005 ◽  
Vol 17 (9) ◽  
pp. 129
Author(s):  
E. Camp-Dotlic ◽  
D. Froiland ◽  
K. L. Kind ◽  
H. Irving-Rodgers ◽  
J. G. Thompson ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Protein Detection ◽  
Staining Intensity ◽  
Principal Cells ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Mouse Tissues ◽  
Cervical Dislocation ◽  
The Stability

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors consisting of an α and β subunit. The level of O2 within cells regulates the stability of HIF-1α and HIF-1 is considered the primary mediator of cellular responses to hypoxia, helping restore O2 homeostasis by promoting the expression of hypoxia-sensitive genes involved in cell survival, angiogenesis, cell proliferation and metabolism. There are few published studies investigating the role of HIF-1 protein in mouse tissues using immunohistochemistry, due to the lack of a reliable protocol and the inability of many commercially available antibodies to detect murine HIF-1α protein. We have developed a protocol that has allowed us to analyse the presence and location of HIF-1α protein in the mouse epididymis and found that it was predominantly located in the nucleus of discrete principal cells in the epididymis of mice housed under normoxic conditions and sacrificed by cervical dislocation. Interestingly, a 2.5× increase (P < 0.05) of HIF-1α protein staining intensity in both the nucleus and cytoplasm of principal cells in the epididymis was detected in mice housed under normoxic conditions but sacrificed with CO2 gas, compared to mice sacrificed by cervical dislocation. HIF-1α protein detection was 3-fold increased in the nucleus and cytoplasm of principal cells when mice were exposed to hypoxic conditions (6% O2 for 1 h). Our results demonstrate that murine HIF-1α can be detected in discrete cells under normoxic conditions, suggesting local differences in O2. Acute hypoxic responses, via deliberate exposure or even CO2 euthanasia can significantly upregulate HIF-1α protein levels. Further studies will investigate the role of HIFs and hypoxia in male and female reproductive function.

scholarly journals Interaction of Hydrogen Sulfide with Oxygen Sensing under Hypoxia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Bo Wu ◽  
Huajian Teng ◽  
Li Zhang ◽  
Hong Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Oxygen Sensing ◽  
Protective Role ◽  
Hypoxia Inducible Factors ◽  
Enzymatic Production ◽  
Hypoxic Conditions ◽  
Carotid Bodies ◽  
Genes Expression ◽  
Mercaptopyruvate Sulfurtransferase

Based on the discovery of endogenous H2S production, many in depth studies show this gasotransmitter with a variety of physiological and pathological functions. Three enzymes, cystathionineβ-synthase (CBS), cystathionineγ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST), are involved in enzymatic production of H2S. Emerging evidence has elucidated an important protective role of H2S in hypoxic conditions in many mammalian systems. However, the mechanisms by which H2S senses and responses to hypoxia are largely elusive. Hypoxia-inducible factors (HIFs) function as key regulators of oxygen sensing, activating target genes expression under hypoxia. Recent studies have shown that exogenous H2S regulates HIF action in different patterns. The activation of carotid bodies is a sensitive and prompt response to hypoxia, rapidly enhancing general O2supply. H2S has been identified as an excitatory mediator of hypoxic sensing in the carotid bodies. This paper presents a brief review of the roles of these two pathways which contribute to hypoxic sensing of H2S.

scholarly journals Hypoxia and the Receptor for Advanced Glycation End Products (RAGE) Signaling in Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8153
Author(s):  
Sakshi Taneja ◽  
Stefan W. Vetter ◽  
Estelle Leclerc
Keyword(s):  
Advanced Glycation End Products ◽  
Cellular Response ◽  
Target Genes ◽  
Tumor Biology ◽  
Hypoxia Inducible Factors ◽  
Advanced Glycation ◽  
Hypoxic Conditions ◽  
Glycation End Products ◽  
End Products

Hypoxia is characterized by an inadequate supply of oxygen to tissues, and hypoxic regions are commonly found in solid tumors. The cellular response to hypoxic conditions is mediated through the activation of hypoxia-inducible factors (HIFs) that control the expression of a large number of target genes. Recent studies have shown that the receptor for advanced glycation end products (RAGE) participates in hypoxia-dependent cellular adaptation. We review recent evidence on the role of RAGE signaling in tumor biology under hypoxic conditions.

scholarly journals Deficiency in the p110α subunit of PI3K results in diminished Tie2 expression and Tie2-/-–like vascular defects in mice

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3935-3938 ◽  
Author(s):  
Etienne Lelievre ◽  
Pierre-Marie Bourbon ◽  
Li-Juan Duan ◽  
Robert L. Nussbaum ◽  
Guo-Hua Fong
Keyword(s):  
Tyrosine Kinases ◽  
Branching Morphogenesis ◽  
Vascular Endothelial ◽  
Mouse Development ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

AbstractPhosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development. However, the in vivo role of PI3K during developmental vascularization remains to be defined. Here we demonstrate that mice deficient in the p110α catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced branching morphogenesis in the endocardium, lack of hierarchical order of large and small branches in the yolk sac, and impaired development of anterior cardinal veins. These vascular defects are strikingly similar to those in mice defective in the Tie2 signaling pathway. Indeed, Tie2 protein levels were significantly lower in p110α-deficient mice. Furthermore, RNA interference of p110α in cultured endothelial cells significantly reduced Tie2 protein levels. These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development.

scholarly journals Protective role of estrogen against excessive erythrocytosis in Monge’s disease

2021 ◽  
Vol 53 (1) ◽  
pp. 125-135
Author(s):  
Priti Azad ◽  
Francisco C. Villafuerte ◽  
Daniela Bermudez ◽  
Gargi Patel ◽  
Gabriel G. Haddad
Keyword(s):  
High Altitude ◽  
Messenger Rna ◽  
Target Genes ◽  
Protective Role ◽  
Mrna Levels ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Andean Population

AbstractMonge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features of CMS is excessive erythrocytosis with extremely high hematocrit levels. In the Andean population, CMS prevalence is vastly different between males and females, being rare in females. Furthermore, there is a sharp increase in CMS incidence in females after menopause. In this study, we assessed the role of sex hormones (testosterone, progesterone, and estrogen) in CMS and non-CMS cells using a well-characterized in vitro erythroid platform. While we found that there was a mild (nonsignificant) increase in RBC production with testosterone, we observed that estrogen, in physiologic concentrations, reduced sharply CD235a+ cells (glycophorin A; a marker of RBC), from 56% in the untreated CMS cells to 10% in the treated CMS cells, in a stage-specific and dose-responsive manner. At the molecular level, we determined that estrogen has a direct effect on GATA1, remarkably decreasing the messenger RNA (mRNA) and protein levels of GATA1 (p < 0.01) and its target genes (Alas2, BclxL, and Epor, p < 0.001). These changes result in a significant increase in apoptosis of erythroid cells. We also demonstrate that estrogen regulates erythropoiesis in CMS patients through estrogen beta signaling and that its inhibition can diminish the effects of estrogen by significantly increasing HIF1, VEGF, and GATA1 mRNA levels. Taken altogether, our results indicate that estrogen has a major impact on the regulation of erythropoiesis, particularly under chronic hypoxic conditions, and has the potential to treat blood diseases, such as high altitude severe erythrocytosis.

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