Hyperpolarized<sup>133</sup>Cs is a sensitive probe for real-time monitoring of biophysical environments

Karlsson, Magnus; Ardenkjær-Larsen, Jan Henrik; Lerche, Mathilde Hauge

doi:10.1039/c7cc02943h

Cited by 8 publications

(12 citation statements)

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“…It was evident in initial experiments with 133 Cs dDNP, that under conventional incubation conditions the rate of entry of 133 Cs + into human RBCs would not be of the same order of magnitude as seen with electroporated yeast cells 7 . However, based on experiments with RBCs that had been treated with yoda1, suspended in a sucrose-based medium (with 30 mM 133 Cs + ), the rate of entry would be sufficient for detection under zero-trans conditions 8–10 .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the fact that treatment of the RBCs with yoda1 left the RBCs in most preparations with a non-zero membrane potential implies that they remained intact. Thus, the 133 Cs + exchange was not simply via (reversible) structurally compromised membranes like with electroporated yeast cells 7 .…”

Section: Discussionmentioning

confidence: 99%

“…dDNP is a recently developed technique that increases the sensitivity for detection of many NMR-receptive nuclides by factors of ~10 4 6 . In the context of 133 Cs + , this opened up the possibility of recording transmembrane flux of the cation into cells 7 on a timescale of several seconds and thus determine kinetic rate constants that can provide mechanistic insights into its membrane-transport processes.…”

Section: Introductionmentioning

confidence: 99%

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Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Kuchel

Karlsson

Lerche

et al. 2019

Sci Rep

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Transmembrane flux of Cs+ (a K+ congener) was measured in human red blood cells (RBCs; erythrocytes) on the 10-s time scale. This is the first report on dissolution dynamic nuclear polarization (dDNP) nuclear magnetic resonance (NMR) spectroscopy with this nuclide in mammalian cells. Four technical developments regularized sample delivery and led to high quality NMR spectra. Cation-free media with the Piezo1 (mechanosensitive cation channel) activator yoda1 maximized the extent of membrane transport. First-order rate constants describing the fluxes were estimated using a combination of statistical methods in Mathematica, including the Markov chain Monte Carlo (MCMC) algorithm. Fluxes were in the range 4–70 μmol Cs+ (L RBC)−1 s−1; these are smaller than for urea, but comparable to glucose. Methodology and analytical procedures developed will be applicable to transmembrane cation transport studies in the presence of additional Piezo1 effectors, to other cellular systems, and potentially in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Kuchel

Karlsson

Lerche

et al. 2019

Sci Rep

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“…As the nature of hyperpolarized protein NMR is somewhat differing from established applications, novel possibilities to investigate protein interactions become conceivable. 38,44,45 Among other excellent examples, this has recently been demonstrated at hand of the binding of the extracellular matrix protein osteopontin (OPN) to its ligand heparin. OPN is an intrinsically disordered protein (IDP) that features a disordered yet compacted core region.…”

Section: Applications Of D-dnp For Chemists Biologists and Physicistsmentioning

confidence: 99%

Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts

Jannin

Dumez

Giraudeau

et al. 2019

Journal of Magnetic Resonance

114

129

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Dissolution dynamic nuclear polarization (d-DNP) is a versatile method to enhance nuclear magnetic resonance (NMR) spectroscopy. It boosts signal intensities by four to five orders of magnitude thereby providing the potential to improve and enable a plethora of applications ranging from the real-time monitoring of chemical or biological processes to metabolomics and incell investigations. This perspectives article highlights possible avenues for developments and applications of d-DNP in biochemical and physicochemical studies. It outlines how chemists, biologists and physicists with various fields of interest can transform and employ d-DNP as a powerful characterization method for their research.

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“…These non‐equilibrium spin populations can be achieved artificially by various experimental methods such as dynamic nuclear polarization (DNP), spin‐exchange optical pumping and para‐hydrogen induced polarization (PHIP) . Among these methods, DNP has been extensively used to polarize a wide range of nuclei including 13 C, 15 N, 1 H, 31 P, 29 Si, 19 F, 6 Li, 133 Cs, 89 Y and 107,109 Ag, and it is currently the preferred technique to polarize 13 C‐labeled compounds for metabolic studies …”

Section: Hyperpolarizationmentioning

confidence: 99%

Probing carbohydrate metabolism using hyperpolarized ¹³C‐labeled molecules

et al. 2018

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Glycolysis is a fundamental metabolic process in all organisms. Anomalies in glucose metabolism are linked to various pathological conditions. In particular, elevated aerobic glycolysis is a characteristic feature of rapidly growing cells. Glycolysis and the closely related pentose phosphate pathway can be monitored in real time by hyperpolarized 13 C-labeled metabolic substrates such as 13 C-enriched, deuterated D-glucose derivatives, [2-13 C]-D-fructose, [2-13 C] dihydroxyacetone, [1-13 C]-Dglycerate, [1-13 C]-D-glucono-δ-lactone and [1-13 C] pyruvate in healthy and diseased tissues. Elevated glycolysis in tumors (the Warburg effect) was also successfully imaged using hyperpolarized [U-13 C 6 , U-2 H 7 ]-D-glucose, while the size of the preexisting lactate pool can be measured by 13 C MRS and/or MRI with hyperpolarized [1-13 C]pyruvate. This review summarizes the application of various hyperpolarized 13 C-labeled metabolites to the real-time monitoring of glycolysis and related metabolic processes in normal and diseased tissues. KEYWORDS dynamic nuclear polarization, glycolysis, hyperpolarized 13 C NMR, metabolic probes 1 | INTRODUCTION Glucose is a fundamental source of energy in living cells. It is present in all living organisms and utilized by both aerobic and anaerobic organisms. 1In eukaryotes, oxidation of glucose through glycolysis and the citric acid cycle (or tricarboxylic acid cycle, TCA cycle) yields energy in the form of ATP along with the release of carbon dioxide (CO 2 ) and water. Glycolysis, the breakdown of glucose, includes several reversible and three irreversible (committed) enzymatic reactions leading to the end-product pyruvate (Figure 1). 2,3 The enzymes of the three committed steps in glycolysis are allosterically controlled both positively and negatively. 4-8 Pyruvate is a key metabolic intermediate with many potential fates, including the production of carbohydrates through gluconeogenesis, fatty acids, amino acids or energy (ATP) via acetyl-CoA. Anomalies in glucose metabolism are linked to various pathological conditions, 9-11 so any method that could reliably monitor glucose metabolism in vivo not only would be valuable in fundamental studies of those diseases but could also be a valuable diagnostic biomarker. It has been widely documented that tumors and other rapidly proliferating cells have a dramatic increased rate of glucose uptake and lactate production even in the presence of adequate oxygen supply (the Warburg effect). 9,12,13 In addition, the expression levels of the mono-carboxylate transporters MCT1 and MCT4 are higher in cancer, and this facilitates the export of lactate from cancer cells. Although there is still an ongoing debate about why aerobic glycolysis is advantageous for tumor growth, in general cancer cells modulate glucose uptake as well as several glycolytic enzymes to match their energy demands by rapidly, albeit /journal/nbm 1 of 23 inefficiently, producing ATP in aerobic glycolysis, and to fulfill their increased demand for anabolic intermediates. [14][15]...

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Hyperpolarized¹³³Cs is a sensitive probe for real-time monitoring of biophysical environments

Cited by 8 publications

References 17 publications

Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts

Probing carbohydrate metabolism using hyperpolarized ¹³C‐labeled molecules

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Hyperpolarized133Cs is a sensitive probe for real-time monitoring of biophysical environments

Cited by 8 publications

References 17 publications

Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Rapid zero-trans kinetics of Cs+ exchange in human erythrocytes quantified by dissolution hyperpolarized 133Cs+ NMR spectroscopy

Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts

Probing carbohydrate metabolism using hyperpolarized 13C‐labeled molecules

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Hyperpolarized¹³³Cs is a sensitive probe for real-time monitoring of biophysical environments

Probing carbohydrate metabolism using hyperpolarized ¹³C‐labeled molecules