Impact of molecular charge on GLUT-specific cellular uptake of glucose bioprobes and in vivo application of the glucose bioprobe, GB2-Cy3

Park, Jong-Min; Um, Jung In; Jo, Ala; Lee, Jinho; Jung, Dawoon; Williams, Darren R.; Park, Seung Bum

doi:10.1039/c4cc00955j

Cited by 29 publications

(32 citation statements)

References 20 publications

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“…Glucose uptake was examined by monitoring the uptake of the fluorescent glucose analogue GB2-Cy3, as previously described (Park et al 2014). Zebrafish larvae were exposed to 20 µM GB2-Cy3 for 6 hr and imaged by fluorescence microscopy using a Zeiss Discovery V8/Axio Cam MRC.…”

Section: Glucose Uptake Assaysmentioning

confidence: 99%

Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth

Cox

Tsomides

Yimlamai

et al. 2018

Preprint

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The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that yap-/-mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis: transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in yap-/-mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improved Yap-deficiency phenotypes, indicating functional importance of glucose-fuelled nucleotide biosynthesis. Yapregulated Glut1 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth.Together, our results reveal a central role for Hippo signalling in metabolic homeostasis.

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Section: Glucose Uptake Assaysmentioning

confidence: 99%

Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth

Cox

Tsomides

Yimlamai

et al. 2018

Preprint

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“…Several methods have been proposed to assess the benefits of d ‐glucose functionalization of an anticancer drug. Enhanced uptake is usually demonstrated indirectly, for example by comparing glucose‐functionalized drugs to their aglycon counterparts, or by competitive inhibition experiments with d ‐glucose . However, these methods usually ignore the difference in water solubility between the glycoconjugates and their aglycon analogues, which can have a major influence on the drug uptake, localization, and/or mode‐of‐action for many compounds.…”

Section: Introductionmentioning

confidence: 99%

“…Enhancedu ptake is usually demonstrated indirectly,f or example by comparing glucose-functionalized drugst ot heir aglyconc ounterparts, [6] or by competitive inhibition experiments with d-glucose. [7] However,t hese methods usually ignoret he differencei nw ater solubility between the glycoconjugates and their aglycona nalogues, whichc an have am ajor influence on the drug uptake, localization,a nd/or mode-of-action for many compounds. Comparing the biological effects of ag lycoconjugate on different cell lines with differente xpressions of glucose transporters is another alternative.…”

Section: Introductionmentioning

confidence: 99%

d‐ Versus l‐Glucose Conjugation: Mitochondrial Targeting of a Light‐Activated Dual‐Mode‐of‐Action Ruthenium‐Based Anticancer Prodrug

Lameijer

Hopkins

Brevé

et al. 2016

Chemistry A European J

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Light‐activated ruthenium polypyridyl anticancer prodrugs often suffer from poor water solubility, poor selectivity, and/or ill‐defined intracellular targets. Coordination of the d‐ or l‐glucose thioether ligand 3 (2‐(2‐(2‐(methylthio)ethoxy)ethoxy)ethyl‐β‐glucopyranoside) to the highly lipophilic ruthenium complex [Ru(tpy)(dppn)(H2O)]2+ ([1]2+; dppn=benzo[i]dipyrido‐[3,2‐a:2′,3′‐c]phenazine, tpy=2,2′:6′,2′′‐terpyridine) solved all these problems at once. The two enantiomers of [Ru(tpy)(dppn)(3)][PF6]2, [d‐2][PF6]2 and [l‐2][PF6]2, were soluble in water, which allowed the influence of the chirality of the glucose moiety on uptake, toxicity, and intracellular localization of the prodrug to be probed without changing any other physicochemical properties. Both compounds showed mild, but different, cytotoxicity in A549 (human lung carcinoma) and MCF‐7 (human breast adenocarcinoma) cancer cells in the dark, whereas following low doses of visible light irradiation (3.1 J cm−2 at λ = 454 nm), a similar, but high cytotoxicity (EC50 < 1 μm), was observed. Irrespective of the chirality, both slightly emissive Ru complexes were found in the mitochondria, and two modes of action may contribute to light‐induced cell death: 1) the glucose thioether ligand is photosubstituted by water, thus [1]2+, which interacts with DNA at an exceptionally high 400:1 base pair/Ru ratio, is released; 2) both [1]2+ and [2]2+ produce massive amounts of singlet oxygen, which leads to very efficient photodynamic DNA cleavage.

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“…Therefore ENOblock was used to investigate the role of enolase in glucose homoeostasis. Thus ENOblock was used as a probe to establish a link between the glycolytic enzyme enolase and PEPCK expression and, significantly, was shown to be effective at inducing glucose uptake in vivo using a zebrafish-based assay for glucose flux [25,26]. Thus ENOblock was used as a probe to establish a link between the glycolytic enzyme enolase and PEPCK expression and, significantly, was shown to be effective at inducing glucose uptake in vivo using a zebrafish-based assay for glucose flux [25,26].…”

Section: Enolasementioning

confidence: 99%

Chemical genetics and its application to moonlighting in glycolytic enzymes

Jung

Kim

Williams

2014

Biochemical Society Transactions

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Glycolysis is an ancient biochemical pathway that breaks down glucose into pyruvate to produce ATP. The structural and catalytic properties of glycolytic enzymes are well-characterized. However, there is growing appreciation that these enzymes participate in numerous moonlighting functions that are unrelated to glycolysis. Recently, chemical genetics has been used to discover novel moonlighting functions in glycolytic enzymes. In the present mini-review, we introduce chemical genetics and discuss how it can be applied to the discovery of protein moonlighting. Specifically, we describe the application of chemical genetics to uncover moonlighting in two glycolytic enzymes, enolase and glyceraldehyde dehydrogenase. This led to the discovery of moonlighting roles in glucose homoeostasis, cancer progression and diabetes-related complications. Finally, we also provide a brief overview of the latest progress in unravelling the myriad moonlighting roles for these enzymes.

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Impact of molecular charge on GLUT-specific cellular uptake of glucose bioprobes and in vivo application of the glucose bioprobe, GB2-Cy3

Cited by 29 publications

References 20 publications

Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth

Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth

d‐ Versus l‐Glucose Conjugation: Mitochondrial Targeting of a Light‐Activated Dual‐Mode‐of‐Action Ruthenium‐Based Anticancer Prodrug

Chemical genetics and its application to moonlighting in glycolytic enzymes

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