Glucose starvation alters lipid-linked oligosaccharide biosynthesis in Chinese hamster ovary cells.

Rearick, James I.; Chapman, Ann E.; Kornfeld, Stuart

doi:10.1016/s0021-9258(19)69156-8

Cited by 168 publications

(22 citation statements)

References 27 publications

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“…Another interpretation is that a post-translational defect develops during glucose deprivation, such that maximal stimulation of transporter protein synthesis by insulin is not realized at the level of glucose transport activity. This may be due to partial glycosylation of the glucose transporter [33,[40][41][42][43], interference with post-translation processing or insertion of transporters in the plasma membrane in the glucose-deprived state.…”

Section: Discussionmentioning

confidence: 99%

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

Maher

Harrison

1990

Diabetologia

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Glucose deprivation of L6 myocytes results in the upregulation of glucose transporter activity, protein and mRNA. We have investigated the downregulation of transporter gene expression by glucose and other hexoses in glucose-deprived L6 myocytes. Glucose transport activity was measured as the uptake of 3H-2-deoxyglucose. Transporter protein and mRNA were detected by immunoblot and Northern blot analysis, respectively, with probes to the rat brain glucose transporter. Glucose deprivation of myocytes, in the absence and presence of insulin, increased 3H-2-deoxyglucose uptake, transporter protein and mRNA levels. Refeeding with glucose reversed the glucose deprivation effects on transport activity and mRNA within 12 h, with half-maximal effects at 1-2 mmol/l glucose. Mannose fully substituted for glucose. Refeeding with the non-metabolisable glucose analogues 2-deoxyglucose and 3-0-methylglucose, or with glucosamine or mannitol, downregulated 3H-2-deoxyglucose uptake but had little or no effect on transporter protein and mRNA expression. In contrast, glucose-6-phosphate markedly increased 3H-2-deoxyglucose uptake but partly downregulated transporter mRNA levels, whereas galactose had a small stimulatory effect on both 3H-2-deoxyglucose uptake and transporter mRNA; neither affected transporter protein levels. The transporter mRNA level was not affected by several metabolites (pyruvate, glyceraldehyde, glycerol) and amino acids (alanine, glutamine). These findings indicate that (i) there are independent pathways for hexose regulation of transport activity, protein and mRNA and (ii) down-regulation of transporter mRNA requires metabolism beyond hexose phosphate whereas glucose uptake may be regulated by direct interaction of hexoses with the transporter.

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Section: Discussionmentioning

confidence: 99%

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

Maher

Harrison

1990

Diabetologia

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“…Perhaps this is an indication of a somewhat synchronized change between GDP-Man and UDP(G) in response to the state of balance between sugar uptake and consumption among individuals. [27][28][29] Unlike the UDP(G) species, which require high spectral resolution to deconvolute the M -9.8 multiplet into constituent components, GDP-Man features a standalone M -10.7 signal that is well separated from the neighboring UDP(G) M -9.8 multiplet, and thus is suitable to be an imaging marker. If SNR is not an issue then the M -10.7 signal can be used for monitoring the potential change of tissue GDP-Man with dietary or pharmaceutic interventions.…”

Section: Significance and Implicationsmentioning

confidence: 99%

“…For example, several cell studies showed that glucose deprivation reduces GDP-Man concentrations, which in turn leads to transitory biosynthetic arrest of dolichol-linked oligosaccharides, with underglycosylation in the formed lipid-linked glycans (shift from Glc3Man9GlcNAc2 to Man5GlcNAc2 and Man3GlcNAc2). 15,27,28 Alternatively, it has been demonstrated that the addition of exogenous mannose corrects altered N-glycosylation in fibroblast cells derived from carbohydrate-deficient glycoprotein syndrome, which otherwise show a 3-10-fold decrease in GDP-Man. 29 Interestingly, a 19 F NMR study showed that GDP-FDMan, an analogue of GDP-Man, can be monitored dynamically in cancer cells treated with 2-deoxy-2[ 18 F] fluoro-D-glucose, 30 a widely used radiopharmaceutical for in vivo determination of regional glucose utilization in positron emission tomography, particularly for the measurement of brain activity.…”

Section: Significance and Implicationsmentioning

confidence: 99%

³¹P‐MRS of healthy human brain: Measurement of guanosine diphosphate mannose at 7 T

Ren

Sherry

2021

NMR in Biomedicine

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Guanosine diphosphate mannose (GDP-Man) is the donor substrate required for mannosylation in the synthesis of glycoproteins, glycolipids and the newly discovered glycoRNA. Normal GDP-Man biosynthesis plays a crucial role in support of a variety of cellular functions, including cell recognition, cell communication and immune responses against viruses. Here, we report the detection of GDP-Man in human brain for the first time, using 31 P MRS at 7 T. The presence of GDP-Man is evidenced by the detection of a weak 31 P doublet at À10.7 ppm that can be assigned to the phosphomannosyl group (Pβ) of the GDP-Man molecule. This weak but well-resolved signal lies 0.9 ppm upfield of UDP(G) Pβ-multiplet from a mixture of UDP-Glc, UDP-Gal, UDP-GlcNAc and UDP-GalNAc. In reference to ATP (2.8 mM), the concentration of GDP-Man in human brain was estimated to be 0.02 ± 0.01 mM, about 15-fold lower than the total concentration of UDP(G) (0.30 ± 0.04, N = 17) and consistent with previous reports of UDP-Man in cells and brain tissue extracts measured by highperformance liquid chromatography. The reproducibility of the measured GDP-Man between test and 2-week retest was 21% ± 15% compared with 5% ± 4% for UDP(G) (N = 7). The measured concentrations of GDP-Man and UDP(G) are linearly correlated ([UDP(G)] = 4.3 [GDP-Man] + 0.02, with R = 0.66 and p = 0.0043), likely reflecting the effect of shared sugar precursors, which may vary among individuals in response to variation in nutritional intake and consumption. Given that GDP-Man has another set of doublet (Pα) at À8.3 ppm that overlaps with NAD(H) and UDP(G)-Pα signals, the amount of GDP-Man could potentially interfere with the deconvolution of these mixed signals in composition analysis. Importantly, this new finding may be useful in advancing our understanding of glycosylation and its role in the development of cancer, as well as infectious and neurodegenerative diseases.

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“…The action of G n-T I on (M an)3(GlcNAc)2-Asn-X is the major physiological path in an interesting mouse lymphoma m utant that is unable to make dolichyl monophosphate mannose (Kornfeld et al 1979;Chapm an et al 1980), and it may be the major cells under certain conditions (Rearick et al 1981). Johnston et al (1966Johnston et al ( , 1973 first reported the presence in goat colostrum of a GlcNActransferase acting on otj-acid glycoprotein pretreated with neuraminidase, P-galactosidase and P-A-acetylglucosaminidase.…”

Section: H S C H a C H T E R And O T H E R Smentioning

confidence: 99%

Oligosaccharide branching of glycoproteins: biosynthetic mechanisms and possible biological functions

1982

Phil. Trans. R. Soc. Lond. B

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One of the most striking features of N- and O-glycosyl oligosaccharides and of lipid-linked oligosaccharides is the high degree of branching of these complex structures. Both proteins and nucleic acids are essentially linear structures and are synthesized by template mechanisms. The branched nature of complex carbohydrates dictates a totally different mechanism of biosynthetic control. Although there are undoubtedly many factors controlling this assembly (e.g. subcellular compartmentation, availability of substrates, cations), our laboratory has studied primarily the enzymatic factors that control the assembly of branched N-glycosyl (Asn-GlcNAc type) and O-glycosyl (Ser[Thr]-GalNAc type) oligosaccharides. There are three basic types of control points that appear to direct biosynthesis. (a) There may be two or more enzymes capable of acting on a single common substrate. Control at this juncture is exerted by the relative activities of these enzymes in a particular tissue. (b) Addition of a specific sugar to the growing oligosaccharide may shut off one or more subsequent enzyme steps, thereby 'freezing' the structure at a certain stage in its synthesis. (c) Progression of the pathway may be impossible until a certain key sugar residue is inserted into the growing oligosaccharide chain. Examples of all three types of control occur in the assembly of both N- and O-glycosyl oligosaccharides. This paper discusses our work on the N-acetylglucosaminyltransferases, which initiate branches in N-glycosyl oligosaccharides, as well as some studies on glycosyltransferases that control the assembly of the four basic Ser(Thr)-GalNAc cores. Important features at all stages of control are the three-dimensional shape of the oligosaccharide, the effect of certain key sugar residues on this three-dimensional shape and the stereochemistry of the interaction of oligosaccharides with proteins. From a functional point of view, protein-oligosaccharide interaction is of vital importance not only to enzyme control mechanisms but to a variety of biological problems such as malignancy and cell-cell interactions, differentiation and development, and susceptibility of cells to hormones, drugs and toxins.

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Glucose starvation alters lipid-linked oligosaccharide biosynthesis in Chinese hamster ovary cells.

Cited by 168 publications

References 27 publications

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

³¹P‐MRS of healthy human brain: Measurement of guanosine diphosphate mannose at 7 T

Oligosaccharide branching of glycoproteins: biosynthetic mechanisms and possible biological functions

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Glucose starvation alters lipid-linked oligosaccharide biosynthesis in Chinese hamster ovary cells.

Cited by 168 publications

References 27 publications

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

Hexose specificity for downregulation of HepG2/brain-type glucose transporter gene expression in L6 myocytes

31P‐MRS of healthy human brain: Measurement of guanosine diphosphate mannose at 7 T

Oligosaccharide branching of glycoproteins: biosynthetic mechanisms and possible biological functions

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³¹P‐MRS of healthy human brain: Measurement of guanosine diphosphate mannose at 7 T