scholarly journals Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene

2010 ◽  
Vol 298 (6) ◽  
pp. C1560-C1571 ◽  
Author(s):  
Mounir Chehtane ◽  
Annette R. Khaled
Keyword(s):  
Cell Fate ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Control Cell ◽  
Rapid Decline ◽  
Hexokinase Ii ◽  
Cell Fate Decisions ◽  
Glut 1 ◽  
Interleukin 7 ◽  
Atp Levels

The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in the metabolism of glucose that was attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression of three important regulators of glucose metabolism, the glucose transporter GLUT-1 and two glycolytic enzymes, hexokinase II (HXKII) and phosphofructokinase-1 (PFK-1), using an IL-7-dependent T-cell line and primary lymphocytes. We found that in lymphocytes deprived of IL-7 loss of glucose uptake correlated with decreased expression of HXKII. Readdition of IL-7 to cytokine-deprived lymphocytes restored the transcription of the HXKII gene within 2 h, but not that of GLUT-1 or PFK-1. IL-7-mediated increases in HXKII, but not GLUT-1 or PFK-1, were also observed at the protein level. Inhibition of HXKII with 3-bromopyruvate or specific small-interfering RNA decreased glucose utilization, as well as ATP levels, in the presence of IL-7, whereas overexpression of HXKII, but not GLUT-1, restored glucose retention and increased ATP levels in the absence of IL-7. We conclude that IL-7 controls glucose utilization by regulating the gene expression of HXKII, suggesting a mechanism by which IL-7 supports bioenergetics that control cell fate decisions in lymphocytes.

scholarly journals Context-dependent roles of YAP/TAZ in stem cell fates and cancer

2021 ◽  
Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Cell ◽  
Substantial Portion ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cell Death Pathways ◽  
Multiple Context ◽  
Cancer Cell Survival ◽  
Context Dependent

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

scholarly journals The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

2020 ◽  
Author(s):  
Emma Carley ◽  
Rachel K. Stewart ◽  
Abigail Zieman ◽  
Iman Jalilian ◽  
Diane. E. King ◽  
...  
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Nuclear Lamina ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Linc Complex ◽  
Force Transmission ◽  
Cell Fate Decisions

AbstractWhile the mechanisms by which chemical signals control cell fate have been well studied, how mechanical inputs impact cell fate decisions are not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells, and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.

scholarly journals Subtype-dependent difference of glucose transporter 1 and hexokinase II expression in craniopharyngioma: an immunohistochemical study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoto Mukada ◽  
Masahiko Tosaka ◽  
Nozomi Matsumura ◽  
Rei Yamaguchi ◽  
Masanori Aihara ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Immunohistochemical Analysis ◽  
Braf V600e ◽  
Beta Catenin ◽  
Hexokinase Ii ◽  
Glucose Transporter 1 ◽  
Positive Group ◽  
Glut 1 ◽  
Positive Rate

AbstractPapillary craniopharyngiomas are characterized by the BRAF V600E mutation. Enhancement of glucose metabolism may be involved in the downstream of the BRAF V600E mutation in many types of tumors. Glucose metabolism was investigated in craniopharyngioma using immunohistochemical analysis. The study included 29 cases of craniopharyngioma (18 adamantinomatous type [ACP], 11 papillary type [PCP]). Immunohistochemical analysis was performed with anti-glucose transporter-1 (GLUT-1), anti-hexokinase-II (HK-II), anti-BRAF V600E, and anti-beta-catenin antibodies. Expressions of GLUT-1 and HK-II were evaluated using a semiquantitative 4-tiered scale as 0, 1+, 2+, 3+, and divided into negative (0 or 1+) or positive (2+ or 3+) group. GLUT-1 expression level was significantly higher in PCPs than ACPs (0, 1+, 2+, 3+ = 2, 12, 4, 0 cases in ACP, respectively, 0, 1+, 2+, 3+ = 0, 2, 5, 4 in PCP, p = 0.001), and most PCPs were classified into positive group (positive rate, 22.2% [4/18] in ACP, 81.8% [9/11] in PCP; p = 0.003). HK-II expression was also conspicuous in PCPs (0, 1+, 2+, 3+ = 7, 9, 2, 0 cases in ACP, 0, 3, 3, 5 in PCP; p = 0.001), and most of them divided into positive group (positive rate, 11.1% [2/18] in ACP, 72.7% [8/11] in PCP; p = 0.001). Expression patterns of BRAF V600E and beta-catenin reflected the clinicopathological subtypes. Both GLUT-1 and HK-II expressions were prominent in PCP. Glucose metabolism might be more enhanced in PCP than ACP. PCP may use the glucose metabolic system downstream of the BRAF V600E mutant protein.

scholarly journals MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1

2017 ◽  
Vol 216 (9) ◽  
pp. 2715-2729 ◽  
Author(s):  
Ann-Christin Hau ◽  
Britta Moyo Grebbin ◽  
Zsuzsa Agoston ◽  
Marie Anders-Maurer ◽  
Tamara Müller ◽  
...  
Keyword(s):  
Cell Fate ◽  
Integration Site ◽  
Control Cell ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Chromatin Dynamics ◽  
Cell Fate Decisions ◽  
Sequence Of Events ◽  
Undifferentiated Cells ◽  
Mechanistic Basis

Pre–B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site (MEIS) proteins control cell fate decisions in many physiological and pathophysiological contexts, but how these proteins function mechanistically remains poorly defined. Focusing on the first hours of neuronal differentiation of adult subventricular zone–derived stem/progenitor cells, we describe a sequence of events by which PBX-MEIS facilitates chromatin accessibility of transcriptionally inactive genes: In undifferentiated cells, PBX1 is bound to the H1-compacted promoter/proximal enhancer of the neuron-specific gene doublecortin (Dcx). Once differentiation is induced, MEIS associates with chromatin-bound PBX1, recruits PARP1/ARTD1, and initiates PARP1-mediated eviction of H1 from the chromatin fiber. These results for the first time link MEIS proteins to PARP-regulated chromatin dynamics and provide a mechanistic basis to explain the profound cellular changes elicited by these proteins.

scholarly journals Molecular regulation of spermatogonial stem cell renewal and differentiation

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. R169-R187 ◽  
Author(s):  
Juho-Antti Mäkelä ◽  
Robin M Hobbs
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Reproductive Function ◽  
Cell Types ◽  
Supporting Cell ◽  
Cell Populations ◽  
Cell Renewal ◽  
Cellular Interactions ◽  
Cell Fate Decisions

The intricate molecular and cellular interactions between spermatogonial stem cells (SSCs) and their cognate niche form the basis for life-long sperm production. To maintain long-term fertility and sustain sufficiently high levels of spermatogenesis, a delicate balance needs to prevail between the different niche factors that control cell fate decisions of SSCs by promoting self-renewal, differentiation priming or spermatogenic commitment of undifferentiated spermatogonia (Aundiff). Previously the SSC niche was thought to be formed primarily by Sertoli cells. However, recent research has indicated that many distinct cell types within the testis contribute to the SSC niche including most somatic cell populations and differentiating germ cells. Moreover, postnatal testis development involves maturation of somatic supporting cell populations and onset of cyclic function of the seminiferous epithelium. The stochastic and flexible behavior of Aundiff further complicates the definition of the SSC niche. Unlike in invertebrate species, providing a simple anatomical description of the SSC niche in the mouse is therefore challenging. Rather, the niche needs to be understood as a dynamic system that is able to serve the long-term reproductive function and maintenance of fertility both under steady-state and during development plus regeneration. Recent data from us and others have also shown that Aundiff reversibly transition between differentiation-primed and self-renewing states based on availability of niche-derived cues. This review focuses on defining the current understanding of the SSC niche and the elements involved in its regulation.

Automated quantitative analyses (AQUA) of cyclic-AMP-response-element-binding protein (CREB), phosphorylated CREB (pCREB), and ataxia-telangiectasia-mutated protein kinase (ATM) protein expression in patients (pts) undergoing thoracic radiation for locally advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13537-e13537 ◽  
Author(s):  
Bo H. Chao ◽  
Anne M. Traynor ◽  
David T Yang ◽  
Chong Zhang ◽  
Thomas Pier ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Expression ◽  
Cell Fate ◽  
Advanced Nsclc ◽  
Control Cell ◽  
Locally Advanced ◽  
High Dose ◽  
Cell Fate Decisions ◽  
Locally Advanced Nsclc ◽  
Thoracic Radiation

e13537 Background: Increased protein expression of CREB, a DNA damage-regulated transcription factor, has been associated with poor survival in advanced NSCLC. We have demonstrated that exposure of cancer cell lines to low dose ionizing radiation (IR) increased pCREB on a Ser133 residue. However, exposure to high dose IR correlated with pCREB on Ser121 by ATM, a master regulator of the cellular DNA damage response. This unusual bimodal response of CREB to IR, reflected by activation at low doses and attenuation at high doses, suggested that CREB may control cell fate decisions in response to DNA damage. We hypothesized that patterns of protein expression of CREB, pCREB Ser133, and ATM would predict treatment response in pts who have undergone radiotherapy for locally advanced NSCLC. Methods: Diagnostic tumor specimens were obtained from pts who underwent thoracic radiation in a clinical trial for locally advanced NSCLC. Protein expression of CREB, pCREB Ser133, and ATM was assessed by AQUA. Wilcoxon rank sum test was used to assess differences in protein expression. Univariate regression was conducted to evaluate protein expression and clinical outcomes. Kruskal Wallis test was used to assess protein expression and pneumonitis. Results: Sufficient tumor tissue was available for 35 of 79 pts enrolled. Best responses in 6 months included 12% CR, 73% PR, 9% SD, and 6% PD. Pre-treatment protein expression per AQUA analyses of CREB, pCREB Ser133, and ATM were not statistically associated with time to in-field progression, time to out-of-field progression, time to distant metastasis, best response, pneumonitis, or overall survival. Unexpectedly, increased expression of pCREB Ser133 was associated with durable anti-tumor response to radiation at a median duration of 14.6 months (p=0.03). Conclusions: Protein expression per AQUA of CREB, pCREB Ser133, and ATM did not confirm our hypotheses, possibly related to our limited sample size. Further analysis of the role of CREB in response to IR in cancer pts is ongoing.

Effects of selective hyperglycemia and hyperinsulinemia on glucose transporters in fetal ovine skeletal muscle

2001 ◽  
Vol 281 (4) ◽  
pp. R1256-R1263 ◽  
Author(s):  
Marianne S. Anderson ◽  
Jing He ◽  
Judy Flowers-Ziegler ◽  
Sherin U. Devaskar ◽  
William W. Hay
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Temporal Correlation ◽  
Utilization Rate ◽  
Fetal Sheep ◽  
Transporter Proteins ◽  
Glut 1 ◽  
Glut 4 ◽  
Glucose Transporter Proteins

We measured net fetal glucose uptake rate from the placenta, shown previously to be equal to total fetal glucose utilization rate (GURf) and proportional to fetal hindlimb skeletal muscle glucose utilization, under normal conditions and after 1, 2.5, and 24 h of selective hyperglycemia (↑G) or selective hyperinsulinemia (↑I). We simultaneously measured the amount of Glut 1 and Glut 4 glucose transporter proteins in fetal sheep skeletal muscle. With ↑G, GURf was increased ∼40% at 1 and 2.5 h but returned to the control rate by 24 h. This transient ↑G-specific ↑GURf was associated with increased plasma membrane-associated Glut 1 (4-fold) and intracellular Glut 4 (3-fold) protein beginning at 1 h. With ↑I, GURf was increased ∼70% at 1, 2.5, and 24 h. This more sustained ↑I-specific ↑GURf was associated with a significant increase in Glut 4 protein (2-fold) at 2.5 h but no change in Glut 1 protein. These results show that ↑G and ↑I have independent effects on the amount of Glut 1 and Glut 4 glucose transporter proteins in ovine fetal skeletal muscle. These effects are time dependent and isoform specific and may contribute to increased glucose utilization in fetal skeletal muscle. The lack of a sustained temporal correlation between the increase in transporter proteins and glucose utilization rates indicates that subcellular localization and activity of a transporter or tissues other than the skeletal muscle contribute to net GURf.

GLUT-1 reduces hypoxia-induced apoptosis and JNK pathway activation

2000 ◽  
Vol 278 (5) ◽  
pp. E958-E966 ◽  
Author(s):  
Zhiwu Lin ◽  
Joel M. Weinberg ◽  
Ricky Malhotra ◽  
Steven E. Merritt ◽  
Lawrence B. Holzman ◽  
...  
Keyword(s):  
Cell Death ◽  
Glucose Uptake ◽  
Cell Lines ◽  
Glucose Transporter ◽  
Morphological Changes ◽  
Control Cell ◽  
Jnk Pathway ◽  
Glut 1 ◽  
Pathway Activation ◽  
Induced Apoptosis

Many studies have suggested that enhanced glucose uptake protects cells from hypoxic injury. More recently, it has become clear that hypoxia induces apoptosis as well as necrotic cell death. We have previously shown that hypoxia-induced apoptosis can be prevented by glucose uptake and glycolytic metabolism in cardiac myocytes. To test whether increasing the number of glucose transporters on the plasma membrane of cells could elicit a similar protective response, independent of the levels of extracellular glucose, we overexpressed the facilitative glucose transporter GLUT-1 in a vascular smooth muscle cell line. After 4 h of hypoxia, the percentage of cells that showed morphological changes of apoptosis was 30.5 ± 2.6% in control cells and only 6.0 ± 1.1 and 3.9 ± 0.3% in GLUT-1-overexpressing cells. Similar protection against cell death and apoptosis was seen in GLUT-1-overexpressing cells treated for 6 h with the electron transport inhibitor rotenone. In addition, hypoxia and rotenone stimulated c-Jun-NH2-terminal kinase (JNK) activity >10-fold in control cell lines, and this activation was markedly reduced in GLUT-1-overexpressing cell lines. A catalytically inactive mutant of MEKK1, an upstream kinase in the JNK pathway, reduced hypoxia-induced apoptosis by 39%. These findings show that GLUT-1 overexpression prevents hypoxia-induced apoptosis possibly via inhibition of stress-activated protein kinase pathway activation.

Mouse Serrate-1 (Jagged-1): expression in the developing tooth is regulated by epithelial-mesenchymal interactions and fibroblast growth factor-4

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1473-1483 ◽  
Author(s):  
T.A. Mitsiadis ◽  
D. Henrique ◽  
I. Thesleff ◽  
U. Lendahl
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Fate ◽  
Tooth Development ◽  
Expression Patterns ◽  
Control Cell ◽  
Fibroblast Growth ◽  
Down Regulation ◽  
Cell Fate Decisions ◽  
Dental Epithelium

Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we analyse the regulation of the mouse Serrate-1 gene during embryogenesis. The Serrate-1 gene is expressed from embryonic day 7.5 (E7.5) and expression is often observed at sites of epithelial-mesenchymal interactions, including the developing tooth, where Serrate-1 is first (E11.5) expressed in all cells of the dental epithelium, but not in mesenchyme. A transient upregulation in dental mesenchyme (E12.5-15.5) is correlated with down-regulation of Serrate-1 expression in epithelial cells contacting the mesenchyme, i.e. in the cells destined to become ameloblasts. This expression pattern is reproduced in explants of dental epithelium and mesenchyme in vitro: epithelium induces Serrate-1 expression in mesenchyme, while epithelium in close proximity to this mesenchyme does not express detectable levels of Serrate-1 mRNA, suggesting that down-regulation of Serrate-1 expression in preameloblasts is caused by mesenchyme-derived signals. Finally, regulation of Serrate-1 expression differs from that of Notch genes. The Serrate-1 gene is induced in dental mesenchyme by fibroblast growth factor-4, but not by bone morphogenetic proteins, while the converse is true for Notch genes. This indicates that, at least during tooth development, the expression patterns observed for receptors and ligands in the Notch signaling pathway are generated by different induction mechanisms.

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