Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours

Durany, Núria; Joseph, Joan; Cruz-Sánchez, F. F.; Carreras, José

doi:10.1038/bjc.1997.525

Cited by 23 publications

(13 citation statements)

References 52 publications

(39 reference statements)

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“…Tumor formation is correlated with a reduction of the 2,3-BPG-synthesizing enzyme 2,3-bisphosphoglycerate mutase (E.C. 5.4.2.4) (37)(38)(39)(40)(41). Because tumor cells are characterized by high glycolytic rates although 2,3-BPG is not detectable, another 2,3-BPG-independent PGM-activating mechanism can be postulated.…”

Section: Effect Of Extracellular Pyruvate On the Pgmtide-induced Inhimentioning

confidence: 99%

Phosphoglycerate Mutase-derived Polypeptide Inhibits Glycolytic Flux and Induces Cell Growth Arrest in Tumor Cell Lines

Engel

Mazurek

Eigenbrodt

et al. 2004

Journal of Biological Chemistry

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The putative tumor metastasis suppressor protein Nm23-H1 is a nucleoside diphosphate kinase that exhibits a novel protein kinase activity when bound to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In this study we show that the glycolytic enzyme phosphoglycerate mutase B (PGM) becomes phosphorylated in the presence of the Nm23-H1⅐GAPDH complex in vitro. Mutation of His-10 in PGM abolishes the Nm23-H1⅐GAPDH complex-induced phosphorylation. Nm23-H1, GAPDH, and PGM are known to co-localize as shown by free flow isoelectric focusing. In association with Nm23-H1 and GAPDH, PGM could be activated by dCTP, which is a substrate of Nm23-H1, in addition to the well known PGM activator 2,3-bisphosphoglycerate. A synthetic cell-penetrating peptide (PGMtide) encompassing the phosphorylated histidine and several residues from PGM (LIRHGE) promoted growth arrest of several tumor cell lines, whereas proliferation of tested non-tumor cells was not influenced. Analysis of metabolic activity of one of the tumor cell lines, MCF-7, indicated that PGMtide inhibited glycolytic flux, consistent with in vivo inhibition of PGM. The specificity of the observed effect was further determined experimentally by testing the effect of PGMtide on cells growing in the presence of pyruvate, which helps to compensate PGM inhibition in the glycolytic pathway. Thus, growth of MCF-7 cells was not arrested by PGMtide in the presence of pyruvate. The data presented here provide evidence that inhibition of PGM activity can be achieved by exogenous addition of a polypeptide, resulting in inhibition of glycolysis and cell growth arrest in cell culture.

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Section: Effect Of Extracellular Pyruvate On the Pgmtide-induced Inhimentioning

confidence: 99%

Phosphoglycerate Mutase-derived Polypeptide Inhibits Glycolytic Flux and Induces Cell Growth Arrest in Tumor Cell Lines

Engel

Mazurek

Eigenbrodt

et al. 2004

Journal of Biological Chemistry

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“…28,29 Brain tumours possessed lower PGM activity than normal brain. 30 In fibroblasts, exposure of the cells to hypoxia induces induction of PGM activity, concomitant with elevations of mRNA and the protein levels of PGM-B, indicating that the enzyme activity is regulated mainly at the transcriptional step. 31 Thus, the colorectal cancer specimens analyzed in our study were expected to have high PGM-B contents.…”

Section: Discussionmentioning

confidence: 97%

Purification and identification of monoubiquitin-phosphoglycerate mutase B complex from human colorectal cancer tissues

et al. 2001

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Ubiquitin-conjugated proteins in human colorectal cancer tissues were analyzed by the immunoprecipitation with the antibody FK2 against conjugated ubiquitin followed with SDS-PAGE. In these immunoprecipitable proteins, a 38-kDa protein was abundant in the tumor regions but almost absent in the adjacent normal regions in 17/26 patients, thus we attempted to purify it. Using immunoaffinity chromatography with the antibody FK2 followed by gel filtration and SDS-PAGE, approximately 10 pmol of this protein was separated from 34 g of the pooled cancerous tissue and transferred onto a PVDF membrane. The 38-kDa protein was further digested with Achromobacter protease I, resulting in several peptide fragments. Amino acid sequences of these peptides showed complete sequence identity to those derived from either ubiquitin or phosphoglycerate mutase-B, suggesting that the 38-kDa protein is monoubiquitinated phosphoglycerate mutase-B, whose calculated mass is 37,369 Da. Western blot using an antibody against phosphoglycerate mutase-B revealed the presence of the 38-kDa protein in the anti-ubiquitin immunoprecipitates derived from the tumor regions, but not from normal counterparts. In addition, part of non-ubiquitinated phosphoglycerate mutase-B (29 kDa) was also found in the anti-ubiquitin immunoprecipitates, whose levels were higher in the tumor regions than in the adjacent normal regions. These results suggest that monoubiquitination of phosphoglycerate mutase-B as well as formation of a noncovalent complex containing ubiquitin and phosphoglycerate mutase-B increases in colorectal cancer and novel modification of phosphoglycerate mutase-B might have a pathophysiological role. © 2001 Wiley-Liss, Inc. Key words: phosphoglycerate mutase; monoubiquitination; affinity chromatography; immunoprecipitationThe eukaryotic modifier protein, ubiquitin is involved in degradation and regulation of intracellular substrate proteins. 1,2 This process involves multiple steps. 3,4 First, ubiquitin is activated by the ubiquitin-activating enzyme (E1). Second, 1 of ubiquitinconjugating enzymes (E2s) transfers ubiquitin from E1 to the substrate that is bound to 1 of ubiquitin-protein ligases (E3s). Third, these enzymes catalyze covalent attachment of ubiquitin to the protein substrate, forming the monoubiquitinated protein. In many cases, additional activated ubiquitin moieties are successively transferred to the previously conjugated ubiquitin molecule, forming a multiubiquitin chain adduct. Furthermore, the multiubiquitinated proteins are destined for degradation by 26S proteasome and this proteolytic machinery plays a fundamental role in various cellular events including cell-cycle progression 2,5,6 and apoptosis. 7,8 The monoubiquitin adducts have distinct functions, e.g., a trigger for endocytosis of plasma membrane proteins, thereby regulating growth factor-derived signal input. 9 The ubiquitin-mediated system is often the target of cancer-related deregulation and can underlie carcinogenesis processes 10 and its proteolytic activities ar...

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“…During glycolysis, PGM catalyzes the interconversion of 3-phosphoglycerate to 2-phosphoglycerate, and then α-enolase catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate [28]. PGM1 is one of the PGM isozymes, and α-enolase is a subunit of enolase.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

Kang

Choi²,

Kim³

et al. 2016

Dev Neurosci

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Environmental enrichment (EE) is a typical experimental method that promotes levels of novelty and complexity that enhance experience-dependent neuroplasticity and cognitive behavior function in laboratory animals. Early EE is associated with resilience in the face of later-life challenges. Since increased synaptic activity enhances endogenous neuronal antioxidant defenses, we hypothesized that long-term EE beginning at an early stage may alter the levels of oxidative stress. We investigated global protein expression and oxidative stress in hippocampal proteins from rats nurtured for a 6-month EE beginning in the prenatal period. The analysis of protein expression was carried out using 2-dimensional gel electrophoresis with matrix-associated laser desorption ionization time-of-flight mass spectrometry. Proteins with altered expression were involved in energy metabolism (phosphoglycerate mutase 1, α-enolase isoform 1, adenylate kinase 1, and triose phosphate isomerase) and antioxidant enzymes (superoxide dismutase 1, glutathione S-transferase ω type 1, peroxiredoxin 5, DJ-1, and glial maturation factor β). Using Western blot assays, some of the proteins with altered expression and NADPH oxidase 2 were confirmed to be decreased. Further confirmation was demonstrated with attenuated expression of 7,8-dihydro-8-oxo-deoxyguanine, a DNA oxidative stress marker, in the hippocampus of EE group rats. Our data demonstrate that a long-term EE program beginning in the prenatal and early postnatal phase of development modulates energy metabolism and reduced oxidant stress possibly through enhanced synaptic activity. We provide evidence that EE can be developed as a tool to protect the brain from oxidative stress-induced injury.

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Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours

Cited by 23 publications

References 52 publications

Phosphoglycerate Mutase-derived Polypeptide Inhibits Glycolytic Flux and Induces Cell Growth Arrest in Tumor Cell Lines

Phosphoglycerate Mutase-derived Polypeptide Inhibits Glycolytic Flux and Induces Cell Growth Arrest in Tumor Cell Lines

Purification and identification of monoubiquitin-phosphoglycerate mutase B complex from human colorectal cancer tissues

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

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