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Current Biology : CB Aug 2022Starch metabolism is linked to plant growth, yet blocking its biosynthesis has species-specific consequences. In a new study, plastidial phosphoglucomutase is knocked...
Starch metabolism is linked to plant growth, yet blocking its biosynthesis has species-specific consequences. In a new study, plastidial phosphoglucomutase is knocked out in aspen trees using CRISPR-Cas9, limiting starch production and altering photosynthesis, but growth, bud break and wood production proceed unaffected.
Topics: Carbohydrate Metabolism; Photosynthesis; Plant Leaves; Plastids; Starch; Trees
PubMed: 35998602
DOI: 10.1016/j.cub.2022.07.024 -
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 -
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 -
Therapeutic Advances in Rare Disease 2023Phosphoglucomutase-1-congenital disorder of glycosylation (PGM1-CDG) (OMIM: 614921) is a rare autosomal recessive inherited metabolic disease caused by the deficiency of...
Phosphoglucomutase-1-congenital disorder of glycosylation (PGM1-CDG) (OMIM: 614921) is a rare autosomal recessive inherited metabolic disease caused by the deficiency of the PGM1 enzyme. Like other CDGs, PGM1-CDG has a multisystemic presentation. The most common clinical findings include liver involvement, rhabdomyolysis, hypoglycemia, and cardiac involvement. Phenotypic severity can vary, though cardiac presentation is usually part of the most severe phenotype, often resulting in early death. Unlike the majority of CDGs, PGM1-CDG has a treatment: oral D-galactose (D-gal) supplementation, which significantly improves many aspects of the disorder. Here, we describe five PGM1-CDG patients treated with D-gal and report both on novel clinical symptoms in PGM1-CDG as well as the effects of the D-gal treatment. D-gal resulted in notable clinical improvement in four patients, though the efficacy of treatment varied between the patients. Furthermore, there was a significant improvement or normalization in transferrin glycosylation, liver transaminases and coagulation factors in three patients, creatine kinase (CK) levels in two, while hypoglycemia resolved in two patients. One patient discontinued the treatment due to urinary frequency and lack of clinical improvement. Furthermore, one patient experienced recurrent episodes of rhabdomyolysis and tachycardia even on higher doses of therapy. D-gal also failed to improve the cardiac function, which was initially abnormal in three patients, and remains the biggest challenge in treating PGM1-CDG. Together, our findings expand the phenotype of PGM1-CDG and underline the importance of developing novel therapies that would specifically treat the cardiac phenotype in PGM1-CDG.
PubMed: 37181075
DOI: 10.1177/26330040221150269 -
Brazilian Journal of Microbiology :... Mar 2022Bacterial leaf blight (BLB) disease, caused by Xanthomonas oryzae pv. oryzae (Xoo), causes major annual economic losses around the world. Inorganic copper compounds and...
Bacterial leaf blight (BLB) disease, caused by Xanthomonas oryzae pv. oryzae (Xoo), causes major annual economic losses around the world. Inorganic copper compounds and antibiotics are conventionally used to control BLB disease. They often cause environmental pollution, contributing to adverse effects on human health. Therefore, research is now leading to the search for alternative control methods. Tea tree oil (TTO) is obtained from a traditional medicinal plant, Melaleuca alternifolia, with antibacterial properties. In this study, we found that TTO showed antibacterial activity against Xoo with a minimum inhibitory concentration (MIC) of 18 mg/ml. These antagonistic activities were not limited only to planktonic cells, as further studies have shown that TTO effectively eradicated sessile cells of Xoo in both initial and mature biofilms. Furthermore, it was also observed that TTO reduced various key virulence properties of Xoo, such as swimming, swarming motility, and the production of extracellular polymeric substances, xanthomonadin, and exoenzymes. TTO triggered ROS generation with cell membrane damage as an antibacterial mode of action against Xoo. The in silico study revealed that 1,8-cineole of TTO was effectively bound to two essential proteins, phosphoglucomutase and peptide deformylase, responsible for the synthesis of EPS and bacterial survival, respectively. These antibacterial and anti-virulence activities of TTO against Xoo were further confirmed by an ex vivo virulence assay where TTO significantly reduced the lesion length caused by Xoo on rice leaves. All these data concluded that TTO could be a safe, environment-friendly alternative approach for the comprehensive management of BLB disease.
Topics: Anti-Bacterial Agents; Biofilms; Humans; Oryza; Plant Diseases; Tea Tree Oil; Virulence; Xanthomonas
PubMed: 35001350
DOI: 10.1007/s42770-021-00657-2 -
Food Chemistry Nov 2023This work investigated the ability of 8 potential biomarkers (phosphoglycerate kinase-1 (PGK1), pyruvate kinase-M2 (PKM2), phosphoglucomutase-1 (PGM1), β-enolase (ENO3,...
This work investigated the ability of 8 potential biomarkers (phosphoglycerate kinase-1 (PGK1), pyruvate kinase-M2 (PKM2), phosphoglucomutase-1 (PGM1), β-enolase (ENO3, myosin-binding protein-C (MYBPC1), myosin regulatory light chain-2 (MYLPF), troponin C-1 (TNNC1) and troponin I-1 (TNNI1)) to characterize meat quality by analyzing their relative abundance and enzymatic activity. Two different meat quality groups (Quadriceps femoris (QF) and Longissimus thoracis (LT) muscles) were selected at 24 h postmortem from 100 lamb carcasses. The relative abundance of PKM2, PGK1, PGM1, ENO3, MYBPC1, MYLPF, and TNNI1 was significantly different between LT and QF muscle groups (P < 0.01). Moreover, PKM, PGK, PGM, and ENO activity in LT muscle group was significantly lower than that in QF muscle (P < 0.05). Suggesting that PKM2, PGK1, PGM1, ENO3, MYBPC1, MYLPF, and TNNI1 can be used as robust biomarkers of lamb meat quality, providing the reference for understanding the molecular mechanism of postmortem meat quality formation in future.
Topics: Animals; Sheep; Muscle, Skeletal; Proteins; Red Meat; Meat; Biomarkers
PubMed: 37392625
DOI: 10.1016/j.foodchem.2023.136739 -
PeerJ 2021Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients....
BACKGROUND
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified.
METHODS
miR-1293 expression and its association with LUAD patients' clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model.
RESULTS
We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients' pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression .
CONCLUSIONS
miR-1293 promoted the proliferation, migration and invasion of LUAD cells targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.
PubMed: 34616611
DOI: 10.7717/peerj.12140 -
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 -
Discover Oncology Jul 2022Prostate cancer (PCa) is the most common malignancy in men in developed countries. Prostate-specific antigen (PSA) remains the most widely used serum marker for prostate...
Prostate cancer (PCa) is the most common malignancy in men in developed countries. Prostate-specific antigen (PSA) remains the most widely used serum marker for prostate cancer. Here, we reported that the expression of phosphoglucomutase-like protein 5 (PGM5) is significantly lower in prostate cancer tissue. The low expression of PGM5 and its related gene signature were found to be linked to poor clinical outcome and high Gleason score. In vitro assays showed that overexpression of PGM5 significantly repressed proliferation and migration of prostate cancer cells. GO and pathway analyses showed the enrichment of genes in regulation of cell growth and migration, and pathways related in cancer. Our additional results showed that the downregulation of PGM5 is closely related to DNA methylation. Taken together, our findings provide the first evidence that PGM5 expression is associated with prostate cancer progression. These results also highlight a preclinical rationale that PGM5 represents a prognostic marker and a promising target for new therapeutic strategies in prostate cancer.
PubMed: 35819729
DOI: 10.1007/s12672-022-00525-x -
Genes Jan 2022The polychaete lives exclusively on the walls of deep-sea hydrothermal chimneys along the East Pacific Rise (EPR), and displays specific adaptations to withstand the...
The polychaete lives exclusively on the walls of deep-sea hydrothermal chimneys along the East Pacific Rise (EPR), and displays specific adaptations to withstand the high temperatures and hypoxia associated with this highly variable habitat. Previous studies have revealed the existence of a balanced polymorphism on the enzyme phosphoglucomutase associated with thermal variations, where allozymes 90 and 100 exhibit different optimal activities and thermostabilities. Exploration of the mutational landscape of phosphoglucomutase 1 revealed the maintenance of four highly divergent allelic lineages encoding the three most frequent electromorphs over the geographic range of . This polymorphism is only governed by two linked amino acid replacements, located in exon 3 (E155Q and E190Q). A two-niche model of selection, including 'cold' and 'hot' conditions, represents the most likely scenario for the long-term persistence of these isoforms. Using directed mutagenesis and the expression of the three recombinant variants allowed us to test the additive effect of these two mutations on the biochemical properties of this enzyme. Our results are coherent with those previously obtained from native proteins, and reveal a thermodynamic trade-off between protein thermostability and catalysis, which is likely to have maintained these functional phenotypes prior to the geographic separation of populations across the Equator about 1.2 million years ago.
Topics: Alleles; Animals; Mutation; Phosphoglucomutase; Polychaeta; Polymorphism, Genetic
PubMed: 35205251
DOI: 10.3390/genes13020206