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International Journal of Molecular... Jan 2023Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung...
Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung infections. HIES that is autosomally dominant in the signal transducer and activator of transcription 3 (STAT3), and autosomal recessive mutations in phosphoglucomutase 3 (PGM3) have been reported in humans. An early diagnosis, based on clinical suspicion and immunological assessments, is challenging. Patients' metabolomics, proteomics, and cytokine profiles were compared to DOCK 8-deficient and atopic dermatitis patients. The PGM3 metabolomics profile identified significant dysregulation in hypotaurine, hypoxanthine, uridine, and ribothymidine. The eight proteins involved include bifunctional arginine demethylase and lysyl hydroxylase (JMJD1B), type 1 protein phosphatase inhibitor 4 (PPI 4), and platelet factor 4 which aligned with an increased level of the cytokine GCSF. Patients with STAT3 deficiency, on the other hand, showed significant dysregulation in eight metabolites, including an increase in protocatechuic acid, seven proteins including ceruloplasmin, and a plasma protease C1 inhibitor, in addition to cytokine VEGF being dysregulated. Using multi-omics profiling, we identified the dysregulation of endothelial growth factor (EGFR) and tumor necrosis factor (TNF) signaling pathways in PGM3 and STAT3 patients, respectively. Our findings may serve as a stepping stone for larger prospective HIES clinical cohorts to validate their future use as biomarkers.
Topics: Humans; Immunoglobulin E; Phosphoglucomutase; STAT3 Transcription Factor; Multiomics; Prospective Studies; Job Syndrome; Mutation; Cytokines
PubMed: 36768728
DOI: 10.3390/ijms24032406 -
Journal of Lasers in Medical Sciences 2022There are documents about the biological effects of blue light radiation on different organisms. An understanding of the molecular mechanism of radiation effects on...
There are documents about the biological effects of blue light radiation on different organisms. An understanding of the molecular mechanism of radiation effects on biological samples is an important event which has attracted researchers' attention. Determining the critical dysregulated proteins of following blue light radiation is the aim of this study. 22 differentially expressed proteins of in response to 300 lux of blue light were extracted from the related literature. Experimental, text mining and co-expression connections between the queried proteins were assessed via the STRING database. The maps were compared and the critical proteins were identified. Among the 21 queried proteins, six individuals including heat shock HSP70 protein, 20S proteasome subunit, 26S proteasome subunit P45, Aspartate aminotransferase, phosphopyruvate hydratase, and phosphoglucomutase were highlighted as the critical proteins in response to blue light radiation. The finding indicates that protein homeostasis and glycogen synthesis are affected by blue light radiation. Due to the critical roles of proteins as enzymes and structural elements in life maintenance and involvement of glycogen synthesis in energy consumption, blue light radiation can be considered as a life promotional agent in future investigations.
PubMed: 36743131
DOI: 10.34172/jlms.2022.47 -
Translational Research : the Journal of... Jul 2023Phosphoglucomutase 1 (PGM1) deficiency is recognized as the third most common N-linked congenital disorders of glycosylation (CDG) in humans. Affected individuals...
Phosphoglucomutase 1 (PGM1) deficiency is recognized as the third most common N-linked congenital disorders of glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine, and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. Here we report on left ventricular ejection fraction (LVEF) in 6 individuals with PGM1-CDG. LVEF was pathologically low in most of these individuals and varied between 10% and 65%. To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 gene (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilation similar to those seen in individuals with PGM1-CDG. Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria, which was similar to the ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. In addition, we found decreased mitochondrial function in the heart of KO mice. Transcriptomic analysis of hearts from mutant mice demonstrated a gene signature of DCM. Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of mutant mice, a glycoproteomic analysis unveiled broad glycosylation changes with significant alterations in sarcolemmal proteins including different subunits of laminin-211, which was confirmed by immunoblot analyses. Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype.
Topics: Humans; Animals; Mice; Cardiomyopathy, Dilated; Stroke Volume; Ventricular Function, Left; Glycogen Storage Disease
PubMed: 36709920
DOI: 10.1016/j.trsl.2023.01.004 -
International Journal of Molecular... Jan 2023Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal...
Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of , a phosphoglucomutase that influences sugar metabolism in yeast. In the presence of galactose, when yeast cells are challenged by LiCl, the phosphoglucomutase activity of PGM2p is decreased, causing an increase in the concentration of toxic galactose metabolism intermediates that result in cell sensitivity. Here, we report that the null yeast mutant strains ∆ and ∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that and modulate the translational level of mRNA, and the observed alteration in translation seems to be associated with the 5'-untranslated region (UTR) of mRNA. Furthermore, we observe that and influence, to varying degrees, the translation of other mRNAs that carry different 5'-UTR secondary structures.
Topics: Lithium Chloride; Saccharomyces cerevisiae; RNA, Messenger; Phosphoglucomutase; Galactose; Saccharomyces cerevisiae Proteins; DEAD-box RNA Helicases
PubMed: 36675300
DOI: 10.3390/ijms24021785 -
Annals of Botany Nov 2023Crassulacean acid metabolism (CAM) is a specialized type of photosynthesis characterized by a diel pattern of stomatal opening at night and closure during the day, which...
The starch-deficient plastidic PHOSPHOGLUCOMUTASE mutant of the constitutive crassulacean acid metabolism (CAM) species Kalanchoë fedtschenkoi impacts diel regulation and timing of stomatal CO2 responsiveness.
BACKGROUND AND AIMS
Crassulacean acid metabolism (CAM) is a specialized type of photosynthesis characterized by a diel pattern of stomatal opening at night and closure during the day, which increases water-use efficiency. Starch degradation is a key regulator of CAM, providing phosphoenolpyruvate as a substrate in the mesophyll for nocturnal assimilation of CO2. Growing recognition of a key role for starch degradation in C3 photosynthesis guard cells for mediating daytime stomatal opening presents the possibility that starch degradation might also impact CAM by regulating the provision of energy and osmolytes to increase guard cell turgor and drive stomatal opening at night. In this study, we tested the hypothesis that the timing of diel starch turnover in CAM guard cells has been reprogrammed during evolution to enable nocturnal stomatal opening and daytime closure.
METHODS
Biochemical and genetic characterization of wild-type and starch-deficient RNAi lines of Kalanchoë fedtschenkoi with reduced activity of plastidic phosphoglucomutase (PGM) constituted a preliminary approach for the understanding of starch metabolism and its implications for stomatal regulation in CAM plants.
KEY RESULTS
Starch deficiency reduced nocturnal net CO2 uptake but had negligible impact on nocturnal stomatal opening. In contrast, daytime stomatal closure was reduced in magnitude and duration in the starch-deficient rPGM RNAi lines, and their stomata were unable to remain closed in response to elevated concentrations of atmospheric CO2 administered during the day. Curtailed daytime stomatal closure was linked to higher soluble sugar contents in the epidermis and mesophyll.
CONCLUSIONS
Nocturnal stomatal opening is not reliant upon starch degradation, but starch biosynthesis is an important sink for carbohydrates, ensuring daytime stomatal closure in this CAM species.
Topics: Crassulacean Acid Metabolism; Kalanchoe; Phosphoglucomutase; Carbon Dioxide; Starch; Photosynthesis
PubMed: 36661206
DOI: 10.1093/aob/mcad017 -
Glycobiology Mar 2023During our biochemical characterization of select bacterial phosphatases belonging to the haloacid dehalogenase superfamily of hydrolases, we discovered a strong bias of...
During our biochemical characterization of select bacterial phosphatases belonging to the haloacid dehalogenase superfamily of hydrolases, we discovered a strong bias of Salmonella YidA for glucose-1-phosphate (Glc-1-P) over galactose-1-phosphate (Gal-1-P). We sought to exploit this ability of YidA to discriminate these two sugar-phosphate epimers in a simple coupled assay that could be a substitute for current cumbersome alternatives. To this end, we focused on Gal-1-P uridylyltransferase (GalT) that is defective in individuals with classical galactosemia, an inborn disorder. GalT catalyzes the conversion of Gal-1-P and UDP-glucose to Glc-1-P and UDP-galactose. When recombinant YidA was coupled to GalT, the final orthophosphate product (generated from selective hydrolysis of Glc-1-P by YidA) could be easily measured using the inexpensive malachite green reagent. When this new YidA-based colorimetric assay was benchmarked using a recombinant Duarte GalT variant, it yielded kcat/Km values that are ~2.5-fold higher than the standard coupled assay that employs phosphoglucomutase and glucose-6-phosphate dehydrogenase. Although the simpler design of our new GalT coupled assay might find appeal in diagnostics, a testable expectation, we spotlight the GalT example to showcase the untapped potential of sugar-phosphate phosphatases with distinctive substrate-recognition properties for measuring the activity of various metabolic enzymes (e.g. trehalose-6-phosphate synthase, N-acetyl-glucosamine-6-phosphate deacetylase, phosphofructokinase).
Topics: Humans; Enzyme Assays; Phosphoric Monoester Hydrolases; Sugars; Uridine Diphosphate Glucose; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 36585843
DOI: 10.1093/glycob/cwac085 -
Molecules (Basel, Switzerland) Dec 2022An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic infection. This study aimed to design compounds with a...
An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic infection. This study aimed to design compounds with a new mechanism through competitive inhibitory activity against phosphomannomutase/phosphoglucomutase (PMM/PGM), using in vitro assessment and a computational (in silico) approach. The active site of PMM/PGM was assessed through molecular redocking using L-tartaric acid as the native ligand and other small molecules, such as glucaric acid, D-sorbitol, and ascorbic acid. The docking program set the small molecules to the active site, showing a stable complex formation. Analysis of structural similarity, bioavailability, absorption, distribution, metabolism, excretion, and toxicity properties proved the potential application of ligands as an anti-biofilm. In vitro assessment with crystal violet showed that the ligands could reach up to 95.87% inhibition at different concentrations. The nitrocellulose membrane and scanning electron microscopic visualization showed that the untreated biofilm was denser than the ligand-treated biofilm.
Topics: Pseudomonas aeruginosa; Ligands; Phosphoglucomutase; Catalytic Domain; Biofilms; Anti-Bacterial Agents
PubMed: 36558064
DOI: 10.3390/molecules27248935 -
Genes Nov 2022Sweet potato (Ipomoea batatas), an important root crop, has storage roots rich in starch that are edible and serve as a raw material in bioenergy production. Increasing...
Sweet potato (Ipomoea batatas), an important root crop, has storage roots rich in starch that are edible and serve as a raw material in bioenergy production. Increasing the storage-root starch contents is a key sweet potato breeding goal. Phosphoglucomutase (PGM) is the catalytic enzyme for the interconversion of glucose-6-phosphate and glucose-1-phosphate, precursors in the plant starch synthetic pathway. Plant PGMs have plastidial and cytosolic isoforms, based on their subcellular localization. Here, , containing 22 exons and 21 introns, was cloned from the sweet potato line Xu 781. This gene was highly expressed in the storage roots and leaves, and its expression was induced by exogenous sucrose treatments. The mature IbpPGM protein was successfully expressed in when a 73-aa chloroplastic transit peptide detected in the N-terminus was excised. The subcellular localization confirmed that IbpPGM was localized to the chloroplasts. The low-starch sweet potato cultivar Lizixiang -overexpression lines showed significantly increased starch, glucose, and fructose levels but a decreased sucrose level. Additionally, the expression levels of the starch synthetic pathway genes in the storage roots were up-regulated to different extents. Thus, significantly increased the starch content of the sweet potato storage roots, which makes it a candidate gene for the genetic engineering of the sweet potato.
Topics: Starch; Ipomoea batatas; Phosphoglucomutase; Plant Roots; Plant Breeding; Sucrose
PubMed: 36553501
DOI: 10.3390/genes13122234 -
Frontiers in Oncology 2022A systematic evaluation of the impact of phosphoglucose translocase PGM on the survival prognosis of tumor patients was conducted to understand its impact on tumors so...
OBJECTIVE
A systematic evaluation of the impact of phosphoglucose translocase PGM on the survival prognosis of tumor patients was conducted to understand its impact on tumors so as to improve the quality of survival and to find effective therapeutic targets for tumor patients.
METHODS
The following were searched in the databases China National Knowledge Infrastructure (CNKI), Wanfang, Wipu, PubMed, EMBASE, ScienceDirect, Web of Science, and Cochrane Library: "PGM1", "PGM2", "PGM3", "PGM4", and "PGM5" as Chinese keywords and "PGM1", "PGM2", "PGM3", "PGM4", "PGM5", "PGM1 cancer", "PGM2 cancer", "PGM3 cancer", "PGM4 cancer", "PGM5 cancer", and "phosphoglucomutase". Relevant studies published from the database establishment to April 2022 were collected. Studies that met the inclusion criteria were extracted and evaluated for quality with reference to the Cochrane 5.1.0 systematic evaluation method, and quality assessment was performed using RevMan 5.3 software.
RESULTS
The final results of nine articles and 10 studies with a total of 3,806 patients were included, including 272 patients in the PGM1 group, 541 patients in the PGM2 group, 1,775 patients in the PGM3 group, and 1,585 patients in the PGM5 group. : after determining the results of the nine articles, it was found that the difference was statistically significant with a p-value <0.05 (hazard ratio (HR) = 0.89, 95% CI 0.69-1.09, p = 0.000). To find the sources of heterogeneity, the remaining eight papers were tested after removing the highly sensitive literature, and the results showed I = 26.5%, p < 0.001, a statistically significant difference. The HR for high expression of PGM1 and PGM2 and PGM5 was <1, while the HR for high expression of PGM3 was >1.
CONCLUSION
Although PGM1, PGM2, PGM3, and PGM5 are enzymes of the same family, their effects on tumors are different. High expression of PGM1, PGM2, and PGM5 can effectively prolong the overall survival of patients. In contrast, high expression of PGM3 reduced the overall survival of patients. This study of PGM family enzymes can assist in subsequent tumor diagnosis, treatment, and prognostic assessment.
PubMed: 36544711
DOI: 10.3389/fonc.2022.1060372 -
Plant & Cell Physiology Apr 2023Maltodextrin metabolism is thought to be involved in both starch initiation and degradation. In this study, potato tuber discs from transgenic lines containing antisense...
Maltodextrin metabolism is thought to be involved in both starch initiation and degradation. In this study, potato tuber discs from transgenic lines containing antisense constructs against the plastidial and cytosolic isoforms of α-glucan phosphorylase and phosphoglucomutase were used to evaluate their influences on the conversion of externally supplied glucose-1-phosphate into soluble maltodextrins, as compared to wild-type potato tubers (Solanum tuberosum L. cv. Desiree). Relative maltodextrin amounts analyzed by capillary electrophoresis with laser-induced fluorescence revealed that tuber discs could immediately uptake glucose-1-phosphate and use it to produce maltooligosaccharides with a degree of polymerization of up to 30, as opposed to tubers repressing the plastidial glucan phosphorylase. The results presented here support previous indications that a specific transporter for glucose-1-phosphate may exist in both the plant cells and the plastidial membranes, thereby allowing a glucose-6-phosphate-independent transport. Furthermore, it confirms that the plastidial glucan phosphorylase is responsible for producing longer maltooligosaccharides in the plastids by catalyzing a glucosyl polymerization reaction when glucose-1-phosphate is available. All these findings contribute to a better understanding of the role of the plastidial phosphorylase as a key enzyme directly involved in the synthesis and degradation of glucans and their implication on starch metabolism.
Topics: Solanum tuberosum; Phosphorylases; Plastids; Starch; Plants, Genetically Modified
PubMed: 36542813
DOI: 10.1093/pcp/pcac174