Erythroid glucose transport in health and disease

Guizouarn, Hélène; Allegrini, Benoit

doi:10.1007/s00424-020-02406-0

Cited by 18 publications

(17 citation statements)

References 136 publications

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“…We first focused on hexose/glucose transporters. Erythrocytes obtain energy only through glycolysis, which makes glucose uptake crucial for erythrocyte development and mature erythrocytes (Guizouarn & Allegrini, 2020). Glycolysis provides ATP, essential to fuel ion pumps, and NADH, a powerful reducing agent that prevents heme oxidation.…”

Section: Resultsmentioning

confidence: 99%

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Karayel

Peng

Bludau

et al. 2020

Molecular Systems Biology

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Human erythropoiesis is an exquisitely controlled multistep developmental process, and its dysregulation leads to numerous human diseases. Transcriptome and epigenome studies provided insights into system-wide regulation, but we currently lack a global mechanistic view on the dynamics of proteome and post-translational regulation coordinating erythroid maturation. We established a mass spectrometry (MS)-based proteomics workflow to quantify and dynamically track 7,400 proteins and 27,000 phosphorylation sites of five distinct maturation stages of in vitro reconstituted erythropoiesis of CD34 + HSPCs. Our data reveal developmental regulation through drastic proteome remodeling across stages of erythroid maturation encompassing most protein classes. This includes various orchestrated changes in solute carriers indicating adjustments to altered metabolic requirements. To define the distinct proteome of each maturation stage, we developed a computational deconvolution approach which revealed stagespecific marker proteins. The dynamic phosphoproteomes combined with a kinome-targeted CRISPR/Cas9 screen uncovered coordinated networks of erythropoietic kinases and pinpointed downregulation of c-Kit/MAPK signaling axis as key driver of maturation. Our system-wide view establishes the functional dynamic of complex phosphosignaling networks and regulation through proteome remodeling in erythropoiesis.

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Section: Resultsmentioning

confidence: 99%

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Karayel

Peng

Bludau

et al. 2020

Molecular Systems Biology

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“…The “zeros cancel” and you are left with 5 grams of glucose if the individual has 5 liters of blood. Since red blood cells represent about 40% of the blood volume, and the glucose is in equilibrium, there may be an extra 40% glucose because of the red blood cell reserve ( 8 ). Adding the glucose from the serum and red blood cells totals about 5–10 grams of glucose in the entire bloodstream.…”

Section: How Much Glucose Is In the Blood?mentioning

confidence: 99%

Type 2 Diabetes Mellitus: A Pathophysiologic Perspective

Westman

2021

Front. Nutr.

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Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5–10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.

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“…Since mature RBCs have neither cell nucleus nor mitochondria 5 , they depend on glucose as the sole energy source. In addition to adenosine triphosphate (ATP) production, RBC glycolysis yields nicotinamide adenine dinucleotide as powerful reducing agent that prevents oxidation of the heme moiety and keeps iron in the reduced Fe 2+ state 6 . Accordingly, defects in glucose transport activity are associated with impaired RBC morphology, reduced deformability and shortened lifespan 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-phosphate suppresses GLUT activity through PP2A and counteracts hyperglycemia in diabetic red blood cells

Thomas

Wollnitzke

Ghaderi

et al. 2022

Preprint

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Membrane phospholipids affect GLUT function in RBC but the role of their large intercellular S1P pool is unknown. We show that altering S1P content by intervening in its precursor uptake, synthesis and efflux had major impacts on RBC glucose uptake and glycolysis. We identified the mechanism as direct activation of PP2A by S1P leading to cell-surface GLUT reduction. This mechanism was highly dynamic as it responded to metabolic cues from the environment by regulating intracellular S1P and thereby glucose uptake, hence counteracting pathophysiological conditions such as diabetes. Accordingly, RBC from hyperglycemic mice and humans with diabetes had higher S1P, Sphk1 and PP2A activities, and lower cell-surface GLUTs. Proof of concept is provided by the resistance of RBC lacking the main S1P exporter MFSD2B to pathological HbA1c increases in hyperglycemia. This mechanism may also be functional in other insulin-independent tissues and could be pharmacologically exploited by existing S1P homeostasis-modifying drugs.

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Erythroid glucose transport in health and disease

Cited by 18 publications

References 136 publications

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Type 2 Diabetes Mellitus: A Pathophysiologic Perspective

Sphingosine-1-phosphate suppresses GLUT activity through PP2A and counteracts hyperglycemia in diabetic red blood cells

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