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Fulltext iCLIP identifies novel roles for SAFB1 in regulating RNA processing and neuronal function

Rivers C, Idris J, Scott H, Rogers M, Lee YB, Gaunt J, et al.

BMC Biol, 2015 Dec 22;13:111.
PMID: 26694817 DOI: 10.1186/s12915-015-0220-7

BACKGROUND: SAFB1 is a RNA binding protein implicated in the regulation of multiple cellular processes such as the regulation of transcription, stress response, DNA repair and RNA processing. To gain further insight into SAFB1 function we used iCLIP and mapped its interaction with RNA on a genome wide level.
RESULTS: iCLIP analysis found SAFB1 binding was enriched, specifically in exons, ncRNAs, 3' and 5' untranslated regions. SAFB1 was found to recognise a purine-rich GAAGA motif with the highest frequency and it is therefore likely to bind core AGA, GAA, or AAG motifs. Confirmatory RT-PCR experiments showed that the expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. For example, we found that the isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1 and that the processing of miR-19a from the miR-17-92 cluster was regulated by SAFB1. These data suggest SAFB1 may influence alternative splicing and, using an NCAM1 minigene, we showed that SAFB1 knockdown altered the expression of two of the three NCAM1 alternative spliced isoforms. However, when the AGA, GAA, and AAG motifs were mutated, SAFB1 knockdown no longer mediated a decrease in the NCAM1 9-10 alternative spliced form. To further investigate the association of SAFB1 with splicing we used exon array analysis and found SAFB1 knockdown mediated the statistically significant up- and downregulation of alternative exons. Further analysis using RNAmotifs to investigate the frequency of association between the motif pairs (AGA followed by AGA, GAA or AAG) and alternative spliced exons found there was a highly significant correlation with downregulated exons. Together, our data suggest SAFB1 will play an important physiological role in the central nervous system regulating synaptic function. We found that SAFB1 regulates dendritic spine density in hippocampal neurons and hence provide empirical evidence supporting this conclusion.
CONCLUSIONS: iCLIP showed that SAFB1 has previously uncharacterised specific RNA binding properties that help coordinate the isoform-specific expression of coding and non-coding genes. These genes regulate splicing, axonal and synaptic function, and are associated with neuropsychiatric disease, suggesting that SAFB1 is an important regulator of key neuronal processes.

Matched MeSH terms: Glycoproteins/metabolism
Fulltext Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats

Golbabapour S, Hajrezaie M, Hassandarvish P, Abdul Majid N, Hadi AH, Nordin N, et al.

Biomed Res Int, 2013;2013:974185.
PMID: 23781513 DOI: 10.1155/2013/974185

The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.

Matched MeSH terms: Glycoproteins/metabolism
Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation

Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN

Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077

Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.

Matched MeSH terms: Membrane Glycoproteins/metabolism*
Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors

Taha M, Ismail NH, Imran S, Selvaraj M, Rashwan H, Farhanah FU, et al.

Bioorg Chem, 2015 Aug;61:36-44.
PMID: 26073618 DOI: 10.1016/j.bioorg.2015.05.010

Twenty five 4, 6-dichlorobenzimidazole derivatives (1-25) have been synthesized and evaluated against β-glucuronidase inhibitory activity. The compounds which actively inhibit β-glucuronidase activity have IC50 values ranging between 4.48 and 46.12 μM and showing better than standard d-saccharic acid 1,4 lactone (IC50=48.4 ± 1.25 μM). Molecular docking provided potential clues to identify interactions between the active molecules and the enzyme which further led us to identify plausible binding mode of all the benzimidazole derivatives. This study confirmed that presence of hydrophilic moieties is crucial to inhibit the human β-glucuronidase.

Matched MeSH terms: Glycoproteins/metabolism
Multi-step molecular docking and dynamics simulation-based screening of large antiviral specific chemical libraries for identification of Nipah virus glycoprotein inhibitors

Kalbhor MS, Bhowmick S, Alanazi AM, Patil PC, Islam MA

Biophys Chem, 2021 03;270:106537.
PMID: 33450550 DOI: 10.1016/j.bpc.2020.106537

Nipah virus (NiV) infections are highly contagious and can cause severe febrile encephalitis. An outbreak of NiV infection has reported high mortality rates in Southeast Asian countries including Bangladesh, East Timor, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, Philippines, Thailand and India. Considering the high risk for an epidemic outbreak, the World Health Organization (WHO) declared NiV as an emerging priority pathogen. However, there are no effective therapeutics or any FDA approved drugs available for the treatment of this infection. Among the known nine proteins of NiV, glycoprotein plays an important role in initiating the entry of viruses and attaching to the host cell receptors. Herein, three antiviral databases consisting of 79,892 chemical entities have been computationally screened against NiV glycoprotein (NiV-G). Particularly, multi-step molecular docking followed by extensive molecular binding interactions analyses, binding free energy estimation, in silico pharmacokinetics, synthetic accessibility and toxicity profile evaluations have been carried out for initial identification of potential NiV-G inhibitors. Further, molecular dynamics (MD) simulation has been performed to understand the dynamic properties of NiV-G protein-bound with proposed five inhibitors (G1-G5) and their interactions behavior, and any conformational changes in NiV-G protein during simulations. Moreover, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) based binding free energies (∆G) has been calculated from all MD simulation trajectories to understand the energy contribution of each proposed compound in maintaining and stabilizing the complex binding interactions with NiV-G protein. Proposed compounds showed high negative ∆G values ranging from -166.246 to -226.652 kJ/mol indicating a strong affinity towards the NiV-G protein.

Matched MeSH terms: Glycoproteins/metabolism
Identification of potential complementary serum biomarkers to differentiate prostate cancer from benign prostatic hyperplasia using gel- and lectin-based proteomics analyses

Jayapalan JJ, Ng KL, Razack AH, Hashim OH

Electrophoresis, 2012 Jul;33(12):1855-62.
PMID: 22740474 DOI: 10.1002/elps.201100608

Diagnosis of prostate cancer (PCa) is currently much reliant on the invasive and time-consuming transrectal ultrasound-guided biopsy of the prostate gland, particularly in light of the inefficient use of prostate-specific antigen as its biomarker. In the present study, we have profiled the sera of patients with PCa and benign prostatic hyperplasia (BPH) using the gel- and lectin-based proteomics methods and demonstrated the significant differential expression of apolipoprotein AII, complement C3 beta chain fragment, inter-alpha-trypsin inhibitor heavy chain 4 fragment, transthyretin, alpha-1-antitrypsin, and high molecular weight kininogen (light chain) between the two groups of patients' samples. Our data are suggestive of the potential use of the serum proteins as complementary biomarkers to effectively discriminate PCa from BPH, although this requires further extensive validation on clinically representative populations.

Matched MeSH terms: Glycoproteins/metabolism
Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors

Doustjalali SR, Yusof R, Yip CH, Looi LM, Pillay B, Hashim OH

Electrophoresis, 2004 Jul;25(14):2392-401.
PMID: 15274022

We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.

Matched MeSH terms: Glycoproteins/metabolism
Fulltext Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors

Hsieh CF, Jheng JR, Lin GH, Chen YL, Ho JY, Liu CJ, et al.

Emerg Microbes Infect, 2020 Dec;9(1):1194-1205.
PMID: 32397909 DOI: 10.1080/22221751.2020.1767512

Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, Salvia miltiorrhiza (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and in vivo mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed to be refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.

Matched MeSH terms: Membrane Glycoproteins/metabolism
Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary

Kitahashi T, Ogawa S, Soga T, Sakuma Y, Parhar I

Endocrinology, 2007 Dec;148(12):5822-30.
PMID: 17823257

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Matched MeSH terms: Glycoproteins/metabolism
Fulltext The Role of GnIH in Biological Rhythms and Social Behaviors

Teo CH, Phon B, Parhar I

Front Endocrinol (Lausanne), 2021;12:728862.
PMID: 34566893 DOI: 10.3389/fendo.2021.728862

Gonadotropin-inhibitory hormone (GnIH) was first discovered in the Japanese quail, and peptides with a C-terminal LPXRFamide sequence, the signature protein structure defining GnIH orthologs, are well conserved across vertebrate species, including fish, reptiles, amphibians, avians, and mammals. In the mammalian brain, three RFamide-related proteins (RFRP-1, RFRP-2, RFRP-3 = GnIH) have been identified as orthologs to the avian GnIH. GnIH is found primarily in the hypothalamus of all vertebrate species, while its receptors are distributed throughout the brain including the hypothalamus and the pituitary. The primary role of GnIH as an inhibitor of gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin release is well conserved in mammalian and non-mammalian species. Circadian rhythmicity of GnIH, regulated by light and seasons, can influence reproductive activity, mating behavior, aggressive behavior, and feeding behavior. There is a potential link between circadian rhythms of GnIH, anxiety-like behavior, sleep, stress, and infertility. Therefore, in this review, we highlight the functions of GnIH in biological rhythms, social behaviors, and reproductive and non-reproductive activities across a variety of mammalian and non-mammalian vertebrate species.

Matched MeSH terms: Glycoproteins/metabolism*
Review: Structure, function and evolution of GnIH

Tsutsui K, Osugi T, Son YL, Ubuka T

Gen Comp Endocrinol, 2018 08 01;264:48-57.
PMID: 28754274 DOI: 10.1016/j.ygcen.2017.07.024

Neuropeptides that possess the Arg-Phe-NH2 motif at their C-termini (i.e., RFamide peptides) have been characterized in the nervous system of both invertebrates and vertebrates. In vertebrates, RFamide peptides make a family and consist of the groups of gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), kisspeptin (kiss1 and kiss2), and pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa). It now appears that these vertebrate RFamide peptides exert important neuroendocrine, behavioral, sensory, and autonomic functions. In 2000, GnIH was discovered as a novel hypothalamic RFamide peptide inhibiting gonadotropin release in quail. Subsequent studies have demonstrated that GnIH acts on the brain and pituitary to modulate reproductive physiology and behavior across vertebrates. To clarify the origin and evolution of GnIH, the existence of GnIH was investigated in agnathans, the most ancient lineage of vertebrates, and basal chordates, such as tunicates and cephalochordates (represented by amphioxus). This review first summarizes the structure and function of GnIH and other RFamide peptides, in particular NPFF having a similar C-terminal structure of GnIH, in vertebrates. Then, this review describes the evolutionary origin of GnIH based on the studies in agnathans and basal chordates.

Matched MeSH terms: Glycoproteins/metabolism*
The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index

Ng HF, Chin KF, Chan KG, Ngeow YF

Genome, 2015 Jun;58(6):315-21.
PMID: 26284904 DOI: 10.1139/gen-2015-0028

suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity.

Matched MeSH terms: Membrane Glycoproteins/metabolism
Identification of potential glycoprotein biomarkers in oral squamous cell carcinoma using sweet strategies

Wong YL, Anand R, Yuen KM, Mustafa WMW, Abraham MT, Tay KK, et al.

Glycoconj J, 2021 02;38(1):1-11.
PMID: 33547992 DOI: 10.1007/s10719-021-09973-z

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

Matched MeSH terms: Glycoproteins/metabolism
Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias

Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, et al.

Hematology, 2007 Feb;12(1):33-7.
PMID: 17364990

The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.

Matched MeSH terms: P-Glycoproteins/metabolism*
The application of Artocarpus integer seed lectin-M in the detection and isolation of selective human serum acute-phase proteins and immunoglobulins

Hashim OH, Ahmad F, Shuib AS

Immunol Invest, 2001 May;30(2):131-41.
PMID: 11465670

Champedak (Artocarpus integer) lectin-M is a lectin with high specificity and affinity for the core-mannosyl residues of the N-linked oligosaccharides of glycoproteins. We have studied the interaction of the champedak seed lectin with human serum glycoproteins that were resolved by 2-dimensional (2-D) gel electrophoresis. The lectin demonstrated strong interaction with haptoglobin beta chain, orosomucoid, alpha1-antitrypsin, alpha2-HS glycoprotein, transferrin, hemopexin, alpha1B-glycoprotein, and the heavy chains of IgA, IgM and IgG of the human serum. With exceptions of the heavy chains of the immunoglobulins and alpha1B-glycoprotein, all the other lectin-M-probed glycopeptides are acute-phase proteins. The use of champedak lectin-M to probe for serum glycoproteins that were separated in a 2-D gel electrophoresis and Western blotting technique may be conveniently applied to analyse the acute-phase and humoral immune responses simultaneously. Subjecting human serum to immobilised-lectin-M affinity chromatography was able to isolate intact haptoglobin, alpha1-antitrypsin, alpha1B-glycoprotein, hemopexin and IgA.

Matched MeSH terms: Glycoproteins/metabolism
Fulltext In silico prediction of interaction between Nipah virus attachment glycoprotein and host cell receptors Ephrin-B2 and Ephrin-B3 in domestic and peridomestic mammals

Hoque AF, Rahman MM, Lamia AS, Islam A, Klena JD, Satter SM, et al.

Infect Genet Evol, 2023 Dec;116:105516.
PMID: 37924857 DOI: 10.1016/j.meegid.2023.105516

Nipah virus (NiV) is a lethal bat-borne zoonotic virus that causes mild to acute respiratory distress and neurological manifestations in humans with a high mortality rate. NiV transmission to humans occurs via consumption of bat-contaminated fruit and date palm sap (DPS), or through direct contact with infected individuals and livestock. Since NiV outbreaks were first reported in pigs from Malaysia and Singapore, non-neutralizing antibodies against NiV attachment Glycoprotein (G) have also been detected in a few domestic mammals. NiV infection is initiated after NiV G binds to the host cell receptors Ephrin-B2 and Ephrin-B3. In this study, we assessed the degree of NiV host tropism in domestic and peridomestic mammals commonly found in Bangladesh that may be crucial in the transmission of NiV by serving as intermediate hosts. We carried out a protein-protein docking analysis of NiV G complexes (n = 52) with Ephrin-B2 and B3 of 13 domestic and peridomestic species using bioinformatics tools. Protein models were generated by homology modelling and the structures were validated for model quality. The different protein-protein complexes in this study were stable, and their binding affinity (ΔG) scores ranged between -8.0 to -19.1 kcal/mol. NiV Bangladesh (NiV-B) strain displayed stronger binding to Ephrin receptors, especially with Ephrin-B3 than the NiV Malaysia (NiV-M) strain, correlating with the observed higher pathogenicity of NiV-B strains. From the docking result, we found that Ephrin receptors of domestic rat (R. norvegicus) had a higher binding affinity for NiV G, suggesting greater susceptibility to NiV infections compared to other study species. Investigations for NiV exposure to domestic/peridomestic animals will help us knowing more the possible role of rats and other animals as intermediate hosts of NiV and would improve future NiV outbreak control and prevention in humans and domestic animals.

Matched MeSH terms: Glycoproteins/metabolism
An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic cell density in cervical neoplasia

Hayati AR, Zulkarnaen M

Int J Gynecol Pathol, 2007 Jan;26(1):83-8.
PMID: 17197902

Cervical carcinoma is the second leading cancer in women in Malaysia, after breast cancer. Human papillomavirus (HPV) has been implicated in the development of dysplasia or cervical intraepithelial neoplasia and progression to squamous cell carcinoma. Because of the confinement of the human papillomavirus infection within the epithelial layer, the presence of dentritic cells or Langerhans cells in epithelial layer of the ectocervix is paramount in producing immune response. The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature cells express CD1a and low CD40/80/86. By identifying CD1a and CD83, theoretically, both immature and mature dentritic cell populations can be studied. In view of the facts, we investigated the infiltrating cell density of mature and immature dentritic cells in cervical neoplasia.

Matched MeSH terms: Membrane Glycoproteins/metabolism*
Fulltext Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells

Phang WM, Tan AA, Gopinath SC, Hashim OH, Kiew LV, Chen Y

Int J Med Sci, 2016;13(5):330-9.
PMID: 27226773 DOI: 10.7150/ijms.14341

Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer.

Matched MeSH terms: Glycoproteins/metabolism*
Phospholipid-Protein Structured Membrane for Microencapsulation of DHA Oil and Evaluation of Its In Vitro Digestibility: Inspired by Milk Fat Globule Membrane

Chen Y, Ge H, Zheng Y, Zhang H, Li Y, Su X, et al.

J Agric Food Chem, 2020 Jun 03;68(22):6190-6201.
PMID: 32379465 DOI: 10.1021/acs.jafc.0c01250

The present study aims to design a milk fat globule membrane (MFGM)-inspired structured membrane (phospholipid- and protein-rich) for microencapsulation of docosahexaenoic acid (DHA) oil. DHA-enriched oil emulsions were prepared using different ratios of sunflower phospholipid (SPL), proteins [whey protein concentrate (WPC), soy protein isolate (SPI), and sodium caseinate (SC)], and maltodextrin and spray-dried to obtain DHA microcapsules. The prepared DHA oil emulsions have nanosized particles. SPLs were found to affect the secondary structure of WPC, which resulted in increased exposure of the protein hydrophobic site and emulsion stability. SPL also reduced the surface tension and viscosity of the DHA oil emulsions. In vitro digestion of the spray-dried DHA microcapsules showed that they were able to effectively resist gastric proteolysis and protect their bioactivity en route to the intestine. The DHA microcapsules have a high lipid digestibility in the small intestine with a high DHA hydrolysis efficiency (74.3%), which is higher than that of commercial DHA microcapsules.

Matched MeSH terms: Glycoproteins/metabolism
Inhibitory effects of xanthones on platelet activating factor receptor binding in vitro

Jantan I, Juriyati J, Warif NA

J Ethnopharmacol, 2001 May;75(2-3):287-90.
PMID: 11297865

Nine naturally occurring xanthones were investigated for their platelet activating factor (PAF) receptor binding inhibitory effects using rabbit platelets. 2-(3-methylbut-2-enyl)-1,3,5-trihydoxyxanthone, macluraxanthone, 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)xanthone, 6-deoxyjacareubin and 2-(3-methylbut-2-enyl)-1,3,5,6-terahydroxyxanthone showed strong inhibition with IC50 values of 4.8, 11.0, 21.0, 29.0 and 44.0 microM, respectively. The prenyl group at C-2, the dimethylprop-2-enyl group at C-4 and the hydroxyl group at C-5 are all beneficial to the binding of xanthones to the PAF receptor. The results revealed that xanthones can represent a new class of natural PAF receptor antagonists.

Matched MeSH terms: Platelet Membrane Glycoproteins/metabolism

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