Adenosine triphosphate is a critical determinant for VEGFR signal during hypoxia

Mamun, Abdullah Al; Hayashi, Hisato; Sakima, Miho; Sato, Motohiko

doi:10.1152/ajpcell.00145.2016

Cited by 5 publications

(10 citation statements)

References 42 publications

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“…Cellular ATP was decreased by exposing the cells to hypoxia as reported previously (Fig. 5a) [11], which may be associated with GLUT1 translocation. The cell surface expression of GLUT1 was determined in the presence of antimycin-A or 2-DG, because they decrease cellular ATP even under normoxia (Fig.…”

Section: Decrease Of Atp Triggers Glut1 Translocation To the Plasma Msupporting

confidence: 82%

“…CoCl 2 increased GLUT1 expression ( Fig. 5d) [11]; however, it did not influence intracellular . (a, b) The histograms represent cell counts (Y-axis, linear scale) versus fluorescence intensity (X-axis, log scale).…”

Section: Hif-1α Does Not Induce Glut1 Translocationmentioning

confidence: 85%

“…Realtime PCRs were run on a StepOnePlus system (Applied Biosystems, Foster City, CA). The following primers were used for PCR [11,13]: GLUT1 forward, 5′-CGT CTT CAT CAT CTT CAC TG-3′; GLUT1 reverse, 5′-CTC CTC GGG TGT CTT ATC-3′; GLUT2 forward, 5′-CAC ACA AGA CCT GGA ATT GACA-3′; GLUT2 reverse, 5′-CGG TCA TCC AGT GGA AGA C-3′; GLUT3 forward, 5′-CGG CTT CCT CAT TAC CTTC-3′; GLUT3 reverse, 5′-GGC ACG ACT TAG ACA TTG G-3′; GLUT4 forward, 5′-CTG GGC CTC ACA GTG CTA C-3′; GLUT4 reverse, 5′-GTC AGG CGC TTC AGA CTC TT-3′; GLUT5 forward, 5′-CAT CAC TGT TGG CAT CCT TGTG-3′; GLUT5 reverse, 5′-AGG ATC GGC CAG CCA TCT AC-3′; Kir6.1 forward, 5′-CAA CTG CTG TGT CCA GAT -3′; Kir6.1 reverse, 5′-ATA CGA ATG GTG ATG TTG GA-3′; Kir6.2 forward, 5′-CAT AGG CAT TAG TGT AGT -3′; Kir6.2 reverse, 5′-TTA TAG AAG AGG CAA CTG -3′; SUR1 forward, 5′-CAA CTG CTG TGT CCA GAT -3′; SUR1 reverse, 5′-ATA CGA ATG GTG ATG TTG GA-3′; SUR2A forward, 5′-AAG CAT TCG GTC ATT GTA G-3′; SUR2A reverse, 5′-GCC ACA TAG TAG GTC TGA -3′; SUR2B forward, 5′-TGG AGA GGA TGT GGA GAA -3′; SUR2B reverse, 5′-CTG TAA GAA TGG TGA ATG TGA T-3′; 18S rRNA forward, 5′-GTC TGT GAT GCC CTT AGA TG-3′; and 18S rRNA reverse, 5′-AGC TTA TGA CCC GCA CTT AC-3′.…”

Section: Real-time Pcrmentioning

confidence: 99%

“…The mRNA levels of GLUTs and KATP channel subunits were analyzed by realtime PCR [11,13] inhibited the hypoxia-induced translocation of GLUT1 to the cell surface in both analyses ( Figs. 2a and 3).…”

Section: Table 1 Expression Of Glut1 Glut3 and Katp Channel Subunitmentioning

confidence: 99%

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Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells

et al. 2020

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Glucose uptake and adenosine triphosphate (ATP) generation are important for the survival and growth of endothelial cells. An increase of glucose uptake under hypoxia was previously shown to be associated with the increased expression of glucose transporters (GLUTs). However, the regulation of GLUT trafficking to the cell surface has not been examined in detail. Here, we report the characterization of GLUT1 translocation to the plasma membrane during hypoxia in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1% O2) for 12 h, which significantly induced GLUT1 expression and translocation to the plasma membrane. GLUT1 translocation was associated with a decrease of intracellular ATP by hypoxia. Decreasing ATP levels with antimycin-A and 2-deoxyglucose induced GLUT1 translocation under normoxia. The induction of hypoxia-inducible factor-1α under normoxia did not influence the cell surface expression of GLUT1 or cellular ATP concentration. Interestingly, the translocation of GLUT1 induced by hypoxia was inhibited by the ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, while the mitochondrial KATP channel inhibitor 5-HD did not influence GLUT1 translocation during hypoxia. These observations indicate that a decrease of intracellular ATP triggers GLUT1 translocation to the plasma membrane and is mediated by KATP channels, which would contribute to glucose uptake in HUVECs during hypoxia.

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Section: Decrease Of Atp Triggers Glut1 Translocation To the Plasma Msupporting

confidence: 82%

Section: Hif-1α Does Not Induce Glut1 Translocationmentioning

confidence: 85%

Section: Real-time Pcrmentioning

confidence: 99%

Section: Table 1 Expression Of Glut1 Glut3 and Katp Channel Subunitmentioning

confidence: 99%

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Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells

et al. 2020

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“…Consequently, new hypoxic niches are formed, recapitulating those angiogenic stimuli that further lead to a tortuous neovasculature, which aggravates hypoperfusion and facilitates cancer cells' intravasion [63]. GLUT1 expression increases in EC under hypoxia [64], and hypoxia is essential in mediating GLUT1 trafficking to the plasma membrane of EC [65]. As mentioned, when GLUT1 was expressed by tumour EC in our study, a correlation with the occurrence of lymphovascular invasion and poor prognosis was evident.…”

Section: Discussionsupporting

confidence: 63%

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Afonso

Gonçalves

Costa

et al. 2023

Cancers

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Proliferating cancer cells are able to reprogram their energy metabolism, favouring glycolysis even in the presence of oxygen and fully functioning mitochondria. Research is needed to validate the glycolysis-related proteins as prognostic/predictive biomarkers in urothelial bladder carcinoma (UBC), a malignancy tagged by high recurrence rates and poor response to chemotherapy. Here, we assessed GLUT1, HK2, PFKL, PKM2, phospho-PDH, and LDHA immunoexpression in 76 UBC samples, differentiating among urothelial, fibroblast, and endothelial cells and among normoxic versus hypoxic areas. We additionally studied the functional effects of the HK2 inhibitor 2-deoxy-D-glucose (2DG) in “in vitro” and “in vivo” preclinical UBC models. We showed that the expression of the glycolysis-related proteins is associated with UBC aggressiveness and poor prognosis. HK2 remained as an independent prognostic factor for disease-free and overall survival. 2DG decreased the UBC cell’s viability, proliferation, migration, and invasion; the inhibition of cell cycle progression and apoptosis occurrence was also verified. A significant reduction in tumour growth and blood vessel formation upon 2DG treatment was observed in the chick chorioallantoic membrane assay. 2DG potentiated the cisplatin-induced inhibition of cell viability in a cisplatin-resistant subline. This study highlights HK2 as a prognostic biomarker for UBC patients and demonstrates the potential benefits of using 2DG as a glycolysis inhibitor. Future studies should focus on integrating 2DG into chemotherapy design, as an attempt to overcome cisplatin resistance.

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Overcoming Hypoxia by Multistage Nanoparticle Delivery System to Inhibit Mitochondrial Respiration for Photodynamic Therapy

Xia

Luo

et al. 2019

Adv Funct Materials

149

112

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Hypoxia, as characterized by the low local oxygen, confers on cancer cells resistance to oxygen-consuming photodynamic therapy (PDT). The limited success reached by current approaches harnessing reoxygenation to enhance PDT outcome promotes the reconsideration of the design of the therapeutic approach. In this study, a multistage delivery system capable of reversing hypoxia is demonstrated. Unlike previous strategies that only expect to affect the peripheral tumor tissue, the size-shrinkable system allows those deeply located hypoxia regions to be treated. Specifically, therapeutics, including atovaquone and indocyanine green derivatives that are respectively responsible for oxidative phosphorylation blockage and PDT, are encapsulated in a gelatin nanoparticle, whose structure would rupture to promote deep penetration when facing matrix metallopeptidase 2 enzyme overexpression in tumor tissue. The antihypoxic performance of the platform has been evaluated using a variety of analyses including flow-cytometry assay, immunofluorescence, and micro-positron-emission tomography imaging. Tumor regression in animal models confirms the feasibility and effectiveness of conquering the PDT-resistance through abrogating the oxygen consumption. It is hopeful that such a strategy could shed light on the development of next-generation PDT-adjuvant treatment.

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Adenosine triphosphate is a critical determinant for VEGFR signal during hypoxia

Cited by 5 publications

References 42 publications

Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells

Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Overcoming Hypoxia by Multistage Nanoparticle Delivery System to Inhibit Mitochondrial Respiration for Photodynamic Therapy

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