Accumulation Of Glycoproteins Research Articles

Nutrient availability and stoichiometry mediate microbial effects on soil carbon sequestration in tropical forests

The persistence of soil organic carbon (SOC) is primarily driven by microbial metabolic activities; however, how microbial effects on SOC sequestration are affected by soil nutrient status remains unclear. Here, we conducted a one-year-long in situ soil incubation experiment using mesh bags (with a mesh size of 38 μm, allowing bacterial colonization and fungal hyphal penetration while preventing root penetration). This experiment involved incubating fertile sugarcane soil and infertile sand across an elevational gradient, characterized by diverse climatic and biotic conditions within a tropical forest. Biomarkers, such as phospholipid fatty acids, carbon-, nitrogen-, and phosphorus-acquiring hydrolases, glomalin-related proteins, and amino sugars, were measured to characterize the production and accumulation of microbial biomass, exo-enzymes, extracellular glycoproteins, and microbial necromass. These measurements aimed to elucidate their respective contribution to the sequestration of SOC. We found that Gram-negative bacteria dominated the microbial community composition in fertile soil, and the higher nutrient availability was related to the production and accumulation of microbial necromass via promoting microbial biomass turnover, thus enhancing the accumulation of SOC in fertile soil. This process was negatively associated with phosphorus availability and carbon- and phosphorus-acquiring enzyme activities in fertile soil. In contrast, the SOC accumulation was positively correlated with nitrogen availability and stoichiometry (including C:N and C:P), as well as moisture content in infertile sand. However, more resources were preferentially allocated to stress-tolerant fungi and Gram-positive bacteria under nutrient deficiency in infertile sand used for microbial biomass maintenance, nutrient acquisition, and environmental adaption which further aggravated the consumption of SOC, resulting in SOC loss after one year of field incubation. Our results suggest that microbial effects on SOC persistence are highly context-dependent and nutrient availability-induced changes in microbial communities and microbial resource-allocation strategies are key processes for understanding and predicting the fate of carbon in tropical forest soils.

Предиктори цитолізу гепатоцитів інсулінорезистентних щурів за умов пре- та постнатального йододефіциту

Carbohydrate metabolism markers, thyroid profile indexes, transaminase activity and structural features of liver were studied, taking into account sexual dimorphism, in rats which were keeping on a high-fructose diet under conditions of adequate iodine supply and pre- and postnatal iodine deficiency. It was found that under fructose loading of animals with iodine deficiency the risk of insulin resistance (IR) development increases (HOMA-IR index in insulin-resistant male rats under conditions of pre- and postnatal iodine deficiency increases respectively by 22 and 13% compared to the data in animals that received a high-carbohydrate diet and adequate iodine supply). It is important, that in males and females with IR, the secretion of free triiodothyronine decreased by 36 and 40%, thyroid-stimulating hormone – by 28 and 34%, respectively, compared to the data of intact animals. The development of IR was accompanied by the activation of aminotransferases in blood serum (more in males). In particular, in male rats with IR under conditions of pre- and postnatal iodine deficiency, the activity of aspartate aminotransferase increased by 2.7 and 2.4 times, alanine aminotransferase – by 3.9 and 2.7 times, respectively, which led to a decrease of the de-Ritis index (more significantly against the background of prenatal iodine deficiency – by 25%) in relation to the data in animals that were on a standard diet. The activity of aminotransferases in rats with IR under conditions of iodine deprivation was higher than in animals with isolated iodine deficiency – by 11-56% and IR – by 13-47 %. In animals with IR, the presence of binucleated hepatocytes with a diffuse decrease in the number of glycogen granules in them and accumulation of glycoproteins in the wall of liver vessels were found. The foci of fatty dystrophy and pronounced zonal character of dystrophic processes in hepatocytes were identified in females, diffuse dystrophy prevailed in males. In the cytoplasm of hepatocytes of animals with IR under conditions of prenatal iodine deficiency, the lightening and the granularity, single granules of glycogen were observed. Under these conditions, the average perimeter (by 74%) and area (by three times) of hepatocytes, the average area of nucleus (by 3.1 times), the average perimeter (by 50%) and area (by 66%) of the nucleolus were increased compared to the control values. The structural changes were consistent with an increase of the transaminase activity. Thus, fructose loading and the development of IR acts as a trigger for cytolysis of hepatocytes, which increases under conditions of iodine deficiency, especially prenatal.

Human cytomegalovirus induces neuronal enolase to support virally mediated metabolic remodeling

Viruses depend on cellular metabolic resources to supply the energy and biomolecular building blocks necessary for their replication. Human cytomegalovirus (HCMV), a leading cause of birth defects and morbidity in immunosuppressed individuals, induces numerous metabolic activities that are important for productive infection. However, many of the mechanisms through which these metabolic activities are induced and how they contribute to infection are unclear. We find that HCMV infection of fibroblasts induces a neuronal gene signature as well as the expression of several metabolic enzyme isoforms that are typically expressed in other tissue types. Of these, the most substantially induced glycolytic gene was the neuron-specific isoform of enolase 2 (ENO2). Induction of ENO2 expression is important for HCMV-mediated glycolytic activation as well as for the virally induced remodeling of pyrimidine-sugar metabolism, which provides the glycosyl subunits necessary for protein glycosylation. Inhibition of ENO2 expression or activity reduced uridine diphosphate (UDP)-sugar pools, attenuated the accumulation of viral glycoproteins, and induced the accumulation of noninfectious viral particles. In addition, our data indicate that the induction of ENO2 expression depends on the HCMV UL38 protein. Collectively, our data indicate that HCMV infection induces a tissue atypical neuronal glycolytic enzyme to activate glycolysis and UDP-sugar metabolism, increase the accumulation of glycosyl building blocks, and enable the expression of an essential viral glycoprotein and the production of infectious virions.

Asn215Ser, Ala143Thr, and Arg112Cys variants in α-galactosidase A protein confer stability loss in Fabry’s disease

Alpha galactosidase A (α-GalA) gene contains nine exons localized at the q-arm of the X chromosome. Generally, an α-GalA enzyme is involved in the removal of galactosyl moieties from the glycoproteins and glycolipids. Dysregulation results in the accumulation of glycoproteins as well as glycolipids in various organs leading to Fabry disease (FD). In this study, we examine the impact of Asn215Ser, Ala143Thr and Arg112Cys variants on the α-GalA protein structure contributing to functional dynamic changes in FD. The seven computational pathogenicity prediction methods were used to predict the effects of these variants on the α-GalA protein. The three-dimensional structure of α-GalA variants was modeled with the Swiss Model and Robetta server and validated using a variety of tools. Then, molecular dynamics (MD) simulation was performed to understand the stability and dynamic behavior of the wild-type and variants structures. Most of our analyzed pathogenicity prediction tools showed that Asn215Ser, Ala143Thr and Arg112Cys variants cause a deleterious effect on the α-GalA protein. Further, MD trajectory analysis showed the destabilizing effect of variants on α-GalA structure based on the root mean square deviation, root mean square fluctuation, solvent accessible surface area, the radius of gyration, hydrogen bond, cluster analysis and PCA analysis. This concludes that the presence of these variants could potentially affect the protein functional process of galactosyl moieties removal which might lead to Fabry disease. Communicated by Ramaswamy H. Sarma

Weber's gland immune/histopathology in pediatric recurrent tonsillitis and obstructive tonsillar hypertrophy cases.

Recurrent tonsillitis and obstructive tonsillar hypertrophy are very common in childhood and constitute the two major causes of tonsillectomy in this age group. There is no study in the literature on the immune/histopathological changes in the recurrent and obstructive tonsillar hypertrophy of Weber's glands. In this study, we aimed to histopathologically and immunohistochemically examine the Weber's glands of pediatric patients with recurrent. A total of 63 patients, with 31 patients aged 6-9 who had surgery for recurrent tonsillitis, and 32 patients aged 6-11 years who had surgery for obstructive tonsillar hypertrophy, were included in the study. The removed Weber's glands were included in the obstructive tonsillar hypertrophy or recurrent tonsillitis group according to the patient's clinical diagnosis. All specimens were coded with a numbering method, where only the surgeon knew which patient was in which group. All specimens were evaluated in the same histology center and by the same histologist, unaware of the clinical diagnosis of the patients (blind). The comparison of Weber's gland immunohistochemical parameter scores of the groups revealed that the scores of the RT group were significantly higher for all three parameters (VEGF: t=6.777; p<0.001), (EGFR: t=4.386; p<0.001), (IL-6: t=5.072; p<0.001). The comparison of the groups in terms of inflammation, basement membrane thickening, myoepithelial cell and glycoprotein accumulation revealed significantly higher Weber's gland evaluation scores in the RT group for all four parameters. (inflammation: t=7.794; p<0.001), (basement membrane thickening: t=6.582; p<0.001), [myoepithelial cell: t=3.693; p<0.001), (glycoprotein accumulation: t=5.287; p<0.001)]. Histopathological and immunohistochemical examination of Weber's gland in pediatric recurrent tonsillitis and obstructive tonsillar hypertrophy cases revealed inflammatory changes in both disease groups. As expected, inflammatory manifestations were more common in the recurrent tonsillitis group. Besides, inflammatory changes detected in Weber's glands of obstructive tonsillar hypertrophy cases without a history of tonsillitis may contribute to the Weber's gland hypothesis, which attempts to explain the etiology of peritonsillar abscess.

Could low α-N-acetylgalactosaminidase plasma concentration cause schizophrenia?

Objectives Using a neurodevelopmental approach to examine the aetiology, we predicted an enzyme deficiency to exist at the cellular level and aimed to measure α-N-acetylgalactosaminidase (α-NAGAL) blood levels. Methods The study included 32 patients diagnosed with schizophrenia and 30 healthy controls. The positive and negative syndrome scale (PANSS) was applied to the patients with schizophrenia. Serum α-NAGAL concentrations were measured in blood samples taken from all participants using the human alpha-N-acetylgalactosaminidase ELISA Kit. Results The mean α-NAGAL values of schizophrenic patients are lower than the mean α-NAGAL values of the control group (p = 0.000 < 0.001). Correlation analysis showed that there was a significant relationship between α-NAGAL values and PANSS scores of patients with schizophrenia. PANSS total (r = −0.708, p = 0.000 < 0.001), PANSS positive (r = −0.627, p = 0.000 < 0.001), PANSS negative (r = −0.386, p = 0.029 < 0.05). And a positive moderate correlation was found between the age of onset of the disease and α-NAGAL levels (r = 0.529, p = 0.002 < 0.05). Conclusions Based on the neurodevelopmental hypothesis, the low α-NAGAL concentrations this study found might cause accumulation of glycoproteins in the lysosomes in the central nervous system during the gestational period and then might result in the clinical symptoms of schizophrenia. α-NAGAL may be an important factor in the aetiology of schizophrenia.

State of endothelial function, lipid spectrum and features of coronary vessels structure of rats with obesity and insulin resistance under iodine deficiency conditions

The aim of the study was to investigate the changes of endothelin-1 content, blood lipid spectrum parameters, structural features of coronary vessels of rats with insulin resistance and obesity under conditions of adequate iodine supply and iodine deficiency. For the modeling of insulin resistance, rats were kept on high-fructose, obesity – high-calorie, iodine deficiency – iodine deficiency diets. It was found that the development of insulin resistance, obesity and iodine deficiency was accompanied by an increase of endothelin-1 level in 2.41, 2.31 times and at 80.17% in blood serum, relative to the data in intact animals. Insulin resistance and obesity under conditions of limited iodine supply leads to the significant changes in endothelial dysfunction (increase in the level of endothelin-1 in 3.02 and 2.50 times relative to control and at 67.38 and 39.40% – relative to mono iodine deficiency) and dyslipidemia (increase in the atherogenic factor at 48.08% – 4.20 times relative to isolated insulin resistance, obesity and iodine deficiency). Such changes were consistent with the structural violations. In insulin-resistant animals focal unevenness of the outer and inner contours, their uneven thickness, areas of homogeneous enlightenment were observed under the conditions of iodine deficiency in the arterioles and minor arteries of the myocardium. In obese animals under the conditions of iodine deficiency, the vessels of the microcirculatory bed were dilated and overflown with erythrocytes. Endotheliocytes with nuclei elongated along the wall, in some places there is a swelling of the cytoplasm of endotheliocytes. In the wall of minor arteries there are transparent vacuoles, areas of homogeneous eosinophilia, which are caused by the accumulation of glycoproteins. Thus, the development of insulin resistance and obesity in iodine deficiency is accompanied by more significant changes in endothelial function and an increase in proatherogenic fractions in the blood lipid spectrum, as evidenced by changes in the structural organization of myocardial vessels than with proper iodine supply.

Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme

BackgroundFucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-l-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex.MethodsAll exons and flanking intron regions of FUCA1 were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with fucosidosis. Bioinformatics tools were then used to predict the impacts of novel alterations on the structure and function of proteins. Furthermore, the identified mutations were localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software, which established a function-structure relationship of the FUCA1 proteins.ResultsFour novel mutations were identified in this study. Two patients (P1 and P2) in Families 1 and 2 who had the severe phenotype were homoallelic for the two identified frameshift mutations p.K57Sfs*75 and p.F77Sfs*55, respectively. The affected patient (P3) from Family 3, who had the milder phenotype, was heterozygous for the novel missense mutation p.G332E and the novel splice site mutation c.662+5g>c. We verified that this sequence variation did not correspond to a polymorphism by testing 50 unrelated individuals. Additionally, 16 FUCA1 polymorphisms were identified. The structure prediction analysis showed that the missense mutation p.G332E would probably lead to a significant conformational change, thereby preventing the expression of the FUCA1 protein indeed; the 3D structural model of the FUCA1 protein reveals that the glycine at position 332 is located near a catalytic nucleophilic residue. This makes it likely that the enzymatic function of the protein with p.G332E is severely impaired.ConclusionThese are the first FUCA1 mutations identified in Tunisia that cause the fucosidosis disease. Bioinformatics analysis allowed us to establish an approximate structure–function relationship for the FUCA1 protein, thereby providing better genotype/phenotype correlation knowledge.

The features of metabolism and structural organization of dental system under conditions of experimental insulin resistance

Peculiarities of calcium homeostasis, the activity of energy synthesis enzymes and structural organization of the dental system in rats under conditions of insulin resistance were analyzed. It was found that impaired glucose tolerance is manifested by a decreased mineralizing ability of hard tissues of alveolar processes and teeth, accompanied by a decrease in calcium content in erythrocyte mass and alveolar processes and an increase in acid phosphatase activity in blood serum. In rats with insulin resistance a decrease in the activity of lactate- and succinate dehydrogenase was detected. Degenerative changes were observed in the bone thickness of the dental area of insulin resistant rats, which were accompanied by the development of hypercellularity of the osteogenic layer of periosteum. Reactive changes in the tooth pulp were manifested by a decrease in the area of its loose connective tissue. Hyperplastic changes with the formation of unexpressed acanthotic bands developed in the oral mucosa of experimental animals, the thickness of the basal and granular layers increased against the background of a decrease in the prickle layer of epitheliocytes. In experimental group we observed a decrease in the nuclear cytoplasmic index and an increase in keratin formation in the epithelium. A narrowing of the lumen of capillaries and arterioles of the dental area, hyperplasia of endothelial cells and an increased accumulation of glycoproteins, especially in small arteries, were also detected in experimental group. Thus, altered carbohydrate metabolism leads to the metabolic changes of teeth supporting apparatus and oral mucosa, aggravating the course of insulin resistance with the development of dental system pathology.

Thiopurines activate an antiviral unfolded protein response that blocks influenza A virus glycoprotein accumulation.

Influenza A viruses (IAVs) utilize host shutoff mechanisms to limit antiviral gene expression and redirect translation machinery to the synthesis of viral proteins. Previously, we showed that IAV replication is sensitive to protein synthesis inhibitors that block translation initiation and induce formation of cytoplasmic condensates of untranslated messenger ribonucleoprotein complexes called stress granules (SGs). In this study, using an image-based high-content screen, we identified two thiopurines, 6-thioguanine (6-TG) and 6-thioguanosine (6-TGo), that triggered SG formation in IAV-infected cells and blocked IAV replication in a dose-dependent manner without eliciting SG formation in uninfected cells. 6-TG and 6-TGo selectively disrupted the synthesis and maturation of IAV glycoproteins hemagglutinin (HA) and neuraminidase (NA) without affecting the levels of the viral RNAs that encode them. By contrast, these thiopurines had minimal effect on other IAV proteins or the global host protein synthesis. Disruption of IAV glycoprotein accumulation by 6-TG and 6-TGo correlated with activation of unfolded protein response (UPR) sensors activating transcription factor-6 (ATF6), inositol requiring enzyme-1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), leading to downstream UPR gene expression. Treatment of infected cells with the chemical chaperone 4-phenylbutyric acid diminished thiopurine-induced UPR activation and partially restored the processing and accumulation of HA and NA. By contrast, chemical inhibition of the integrated stress response downstream of PERK restored accumulation of NA monomers but did not restore processing of viral glycoproteins. Genetic deletion of PERK enhanced the antiviral effect of 6-TG without causing overt cytotoxicity, suggesting that while UPR activation correlates with diminished viral glycoprotein accumulation, PERK could limit the antiviral effects of drug-induced ER stress. Taken together, these data indicate that 6-TG and 6-TGo are effective host-targeted antivirals that trigger the UPR and selectively disrupt accumulation of viral glycoproteins.IMPORTANCESecreted and transmembrane proteins are synthesized in the endoplasmic reticulum (ER), where they are folded and modified prior to transport. Many viruses rely on the ER for the synthesis and processing of viral glycoproteins that will ultimately be incorporated into viral envelopes. Viral burden on the ER can trigger the unfolded protein response (UPR). Much remains to be learned about how viruses co-opt the UPR to ensure efficient synthesis of viral glycoproteins. Here, we show that two FDA-approved thiopurine drugs, 6-TG and 6-TGo, induce the UPR, which represents a previously unrecognized effect of these drugs on cell physiology. This thiopurine-mediated UPR activation blocks influenza virus replication by impeding viral glycoprotein accumulation. Our findings suggest that 6-TG and 6-TGo may have broad antiviral effect against enveloped viruses that require precise tuning of the UPR to support viral glycoprotein synthesis.

Protective effects of curcumin on bleomycin-induced changes in lung glycoproteins.

The present study investigated the therapeutic effect of curcumin on bleomycin (BLM)-induced alterations in glycoprotein components in the fibrotic lungs. Analysis of the bronchoalveolar lavage fluid (BALF) demonstrated increased fibronectin content at 3, 5, 7, and 14days after BLM administration. Similarly, lung tissue fibronectin content revealed a progressive increase at various times (days 3, 5, 7, 14, and 28) during the development of lung fibrosis. In addition, alveolar macrophage release of fibronectin was also elevated in BLM-treated rats. Analysis of carbohydrate moieties of glycoproteins revealed an increase in total hexose, fucose, sialic acid and hexosamine levels at 7, 14, and 28days after BLM treatment. Furthermore, the activities of lung glycosidases such as N-acetyl-β-D-glucosaminidase, β-glucosidase, β-galactosidase, and β-fucosidase in the fibrotic rats were elevated. Importantly, curcumin significantly inhibited the BLM-induced increases in BALF and lung fibronectin levels. Treatment of BLM rats with curcumin dramatically suppressed alveolar macrophage release of fibronectin. Curcumin also inhibited the increases in complex carbohydrates and glycosidases in the fibrotic lungs. These findings suggest that BLM-induced lung fibrosis is associated with accumulation of glycoproteins, and curcumin has the ability to suppress the enhanced deposition of glycoproteins in the fibrotic lung.

Stigma receptivity with pollen in sunflower accompanies novel histochemical and biochemical changes in both male and female reproductive structures

Pollen–pistil interaction is one of the widely studied cell–cell communication events in angiosperms. Pollination of the receptive pistil with compatible pollen and the subsequent steps that determines the success of fertilization depend on the cooperative events between pollen and pistil. Before the onset of these interactive events between pollen and pistil, both the participants prepare themselves for the upcoming complex cellular events. Receptive surface of stigma is characterized by the accumulation of reactive oxygen species and expression of specific biomolecules and enzymes, such as non-specific esterases and peroxidases. Pollen grains produce nitric oxide that scavenge reactive oxygen species generated on stigma surface after pollination and just prior to pollen germination. Present work reports accumulation of glycoproteins, lipids and phospholipids at the base of stigmatic papillae in mature receptive stigma. A 31 kDa glycoprotein has been detected in stigma homogenate. Stigma exhibit enhanced expression of peroxidase isoforms relative to buffer soluble fractions of pollen, i.e. intact pollen, internal pollen and tryphine fractions. A 54 kDa protease is expressed in pollen grains as well as stigma. Biochemical analyses of these biomolecules in pollen and stigma relative to other vegetative (corolla of ray and disc floret, bracts, young leaves) and reproductive (anther wall and ovary) parts highlight the implications of these biomolecules in pollen–stigma interaction.

Metabolic syndrome perturbs deglucosylation and reglucosylation in the glycoprotein folding cycle.

Deglucosylation and reglucosylation of glycoproteins by glucosidase II and uridine diphosphate-glucose: glycoprotein glucosyltransferase 1 (UGGT1), respectively, are important steps in glycoprotein quality control. Misfolded glycoprotein accumulation is associated with endoplasmic reticulum stress and can lead to protein misfolding diseases such as metabolic syndrome. Here, we analyzed the expression and activities of glucosidase II and UGGT1 in rat models of obesity and obese type 2 diabetes, and phenotypes associated with moderate and severe metabolic syndrome, respectively. In obesity, the mRNA and protein levels of glucosidase II and UGGT1 are decreased and their activities are reduced. In obese type 2 diabetes, the mRNA and protein levels of these enzymes are increased, and glucosidase II activity is slightly recovered, although UGGT1 activity is reduced. Our findings suggest that metabolic syndrome affects deglucosylation/reglucosylation enzymes according to disease severity.

Co-expression of human calreticulin significantly improves the production of HIV gp140 and other viral glycoproteins in plants.

SummaryPlant molecular farming (PMF) is rapidly gaining traction as a viable alternative to the currently accepted paradigm of producing biologics. While the platform is potentially cheaper and more scalable than conventional manufacturing systems, expression yields and appropriate post‐translational modifications along the plant secretory pathway remain a challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low yields in plants and, in some cases, may not be appropriately processed. Recently, however, transiently or stably engineering the host plant has shown promise as a strategy for producing heterologous proteins with more complex maturation requirements. In this study we investigated the co‐expression of a suite of human chaperones to improve the production of a human immunodeficiency virus (HIV) type 1 soluble gp140 vaccine candidate in Nicotiana benthamiana plants. The co‐expression of calreticulin (CRT) resulted in a dramatic increase in Env expression and ameliorated the endoplasmic reticulum (ER) stress response ‐ as evidenced by lower transcript abundance of representative stress‐responsive genes. The co‐expression of CRT similarly improved accumulation of glycoproteins from Epstein‐Barr virus (EBV), Rift Valley fever virus (RVFV) and chikungunya virus (CHIKV), suggesting that the endogenous chaperone machinery may impose a bottleneck for their production. We subsequently successfully combined the co‐expression of human CRT with the transient expression of human furin, to enable the production of an appropriately cleaved HIV gp140 antigen. These transient plant host engineering strategies are a promising approach for the production of high yields of appropriately processed and cleaved viral glycoproteins.

Asthma-Alleviating Potential of 6-Gingerol: Effect on Cytokines, Related mRNA and c-Myc, and NFAT1 Expression in Ovalbumin-Sensitized Asthma in Rats.

In this study, we aimed at assessing the therapeutical potential of 6-gingerol ([5S]-5-hydroxy-1-[4-hydroxy- 3-methoxyphenyl]-3-decanone) against ovalbumin-sensitized asthma in rats. The rats were treated intraperitoneally with 6-gingerol (75 mg/kg body weight) for 30 days and a theophylline (200 mg/kg body weight)-treated group as a control. Changes in the levels of T-cell-linked cytokines (interleukin-4 [IL-4], IL-5, IL-13, and interferon-gamma [IFN-?]), total immunoglobulin E (IgE), gene expressions of bitter taste-sensing type 2-receptor 10 (T2R10), inositol 1,4,5-triphosphate receptor 1 (IP3R1), Orai1 and protein expressions of nuclear factor of activated T cells 1 (NFAT1), c-Myc and histopathological changes were observed in rats. 6-Gingerol exerts its beneficial impacts like theophylline in lessening IL-4, IL-5, and IL-13, and IgE and increasing the level of IFN-?. Significant down-regulation of T2R10 gene expression and up-regulation of IP3R1 and Orai1 gene expression were observed in experimental rats and these alterations were normalized after treatment with 6-gingerol or theophylline. The histopathological study revealed that the accumulation of glycoprotein and thickness of alveolar epithelium in asthmatic rats and supplementation with 6-gingerol or theophylline in asthmatic rats restored these changes to normal. In conclusion, 6-gingerol has a protective effect on lungs in ovalbumin-sensitized asthma in rats.

Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder

Glucosidase I (GI) removes the outermost glucose from protein-linked Glc3Man9GlcNAc2 (G3M9) in the endoplasmic reticulum (ER). Individuals with congenital disorders of glycosylation MOGS-CDG bear mutations in the GI-encoding gene (gls1). Although GI absence has been reported to produce lethality in Schizosaccharomyces pombe yeasts, here we obtained two viable Δgls1 mutants, one with a very sick but not lethal phenotype (Δgls1-S) and the other with a healthier one (Δgls1-H). The sick strain displayed only G3M9 as an ER protein-linked oligosaccharide, whereas the healthier strain had both G3M9 and Man9GlcNAc2 The lipid-linked oligosaccharide patterns of the two strains revealed that the most abundantly formed glycans were G3M9 in Δgls1-S and Glc2Man9GlcNAc2 in Δgls1-H, suggesting reduced Alg10p glucosyltransferase activity in the Δgls1-H strain. A mutation in the alg10+ gene was indeed observed in this strain. Our results indicated that abrogated G3M9 deglucosylation was responsible for the severe defects observed in Δgls1-S cells. Further studies disclosed that the defects could not be ascribed to disruption of glycoprotein entrance into calnexin-folding cycles, inhibition of the oligosaccharyltransferase by transfer reaction products, or reduced proteasomal degradation of misfolded glycoproteins. Lack of triglucosylated glycoprotein deglucosylation neither significantly prevented glycan elongation in the Golgi nor modified the overall cell wall monosaccharide composition. Nevertheless, it resulted in a distorted cell wall and in the absence of underlying ER membranes. Furthermore, Golgi expression of human endomannosidase partially restored normal growth in Δgls1-S cells. We propose that accumulation of G3M9-bearing glycoproteins is toxic and at least partially responsible for defects observed in MOGS-CDG.

Tissue-specific molecular and cellular toxicity of Pb in the oyster (Crassostrea gigas): mRNA expression and physiological studies

Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues. In the gills, Pb disturbed the protein metabolism, with the most significant enrichment of the “protein processing in endoplasmic reticulum” pathway. The main mechanism comprised of a Pb-stimulated calcium (Ca2+) increase by the up-regulation of transporter-Ca-ATPase expression. The disturbed Ca2+ homeostasis then further induced high expressions of endoplasmic reticulum (ER) chaperones, leading to ER stress in the oysters. Unfolded proteins induced ER associated degradation (ERAD), thereby preventing the accumulation of folding-incompetent glycoproteins. However, Pb mainly induced oxidative reduction reactions in the digestive gland with high accumulation of lipid peroxidation products and high expression of antioxidant enzymes. Further, Pb induced fatty acid β-oxidation and CYP450 catalyzed ω-oxidation due to increased metabolic expenditure for detoxification. The increased content of arachidonic acid indicated that Pb exposure might alter unsaturated fatty acid composition and disturb cellular membrane functions. Taken together, our results provided a new insight into the molecular mechanisms underlying Pb toxicity in oysters.

Non-invasive in vivo Imaging Grading of Liver Fibrosis.

Liver fibrosis (LF), a common consequence of chronic liver diseases with various etiologies, is characterized by excessive accumulation of macromolecules, including collagen, glycoproteins and proteoglycans, in the liver. LF can result in hepatic dysfunction, cirrhosis, portal hypertension and, in some cases, hepatocellular carcinoma. As the current gold standard for diagnosing LF, liver biopsy, however, is invasive and prone to sampling errors and procedure-related complications. Therefore, developing noninvasive, precise and reproducible imaging tests for diagnosing and staging LF is of great significance. Conventional ultrasound (US), computed tomography (CT) and magnetic resonance (MR) imaging can depict morphological alterations of advanced LF, but have relatively limited capability characterizing early-stage LF. In order to optimize the diagnostic performances of noninvasive imaging techniques for LF across its entire spectrum of severity, a number of novel methods, including US elastography, CT perfusion imaging and various MR imaging–based techniques, have been established and introduced to clinical practice. In this review, we intended to summarize current noninvasive imaging techniques for LF, with special emphasis on the possible roles, advantages and limitations of the new emerging imaging modalities.

Health Related Quality of Life, Disability, and Pain in Alpha Mannosidosis

Alpha-mannosidosis, a rare lysosomal storage disorder caused by deficiency of the lysosomal enzyme alpha-mannosidase, results in accumulation of mannose-rich glycoproteins in the tissues and sequel...

The Mechanism of Swainsonine Causing Early Pregnancy Abnormal Decidualization and Inducing Abortion by Changing Glycosylation Modification

Locoweed is a poisonous plant that severely harms the development of grass-land and animal husbandry throughout the world. Oxytropis and Astragalus are the Latin names for the poisonous plants commonly known as locoweed. The main toxic substance in these plants is swainsonine. It is a strong inhibitor of lysosomal α-mannosidase I and Golgi body α-mannosidase II, resulting in the accumulation of oligosaccharides and glycoproteins in lysosomes, interfering with the molecular and cellular recognition of glycans, and causing tissue-cell vacuolar degeneration. Livestock shows a series of clinical and pathological symptoms, mainly for the decline of reproductive performance. The effects in dams are abortion, weak fetus, and fetal malformations. The key step in maintaining pregnancy in dams is early endometrial decidualization, because reproductive hormones, decidual cell apoptosis, endoplasmic reticulum (ER) stress, and other immune factors are negatively affected by swainsonine. This article addresses the modifications that occur through glycan processing and glycosylation resulting in the change of post-translational modification of the protein and the activity of the glycoprotein, and then direct and indirect mechanisms of ER stress, apoptosis, reproductive hormones, immune factors, and cell cycle and other pathways. Our aim is to find new methods of prevention and treatment of swainsonine poisoning in grassland animals.