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Journal of Dental Research Aug 2007The proteome of whole saliva, in contrast to that of serum, is highly susceptible to a variety of physiological and biochemical processes. First, salivary protein... (Review)
Review
The proteome of whole saliva, in contrast to that of serum, is highly susceptible to a variety of physiological and biochemical processes. First, salivary protein secretion is under neurologic control, with protein output being dependent on the stimulus. Second, extensive salivary protein modifications occur in the oral environment, where a plethora of host- and bacteria-derived enzymes act on proteins emanating from the glandular ducts. Salivary protein biosynthesis starts with the transcription and translation of salivary protein genes in the glands, followed by post-translational processing involving protein glycosylation, phosphorylation, and proteolysis. This gives rise to salivary proteins occurring in families, consisting of structurally closely related family members. Once glandular secretions enter the non-sterile oral environment, proteins are subjected to additional and continuous protein modifications, leading to extensive proteolytic cleavage, partial deglycosylation, and protein-protein complex formation. All these protein modifications occur in a dynamic environment dictated by the continuous supply of newly synthesized proteins and removal by swallowing. Understanding the proteome of whole saliva in an environment of continuous turnover will be a prerequisite to gain insight into the physiological and pathological processes relevant to oral health, and be crucial for the identification of meaningful biomarkers for oral disease.
Topics: Humans; Molecular Structure; Multiprotein Complexes; Protein Biosynthesis; Protein Processing, Post-Translational; Proteomics; Saliva; Salivary Proteins and Peptides
PubMed: 17652194
DOI: 10.1177/154405910708600802 -
Cell Reports Jun 2020Vitamin-D-binding protein (DBP) or group-specific component of serum (GC-globulin) carries vitamin D metabolites from the circulation to target tissues. DBP is highly...
Vitamin-D-binding protein (DBP) or group-specific component of serum (GC-globulin) carries vitamin D metabolites from the circulation to target tissues. DBP is highly localized to the liver and pancreatic α cells. Although DBP serum levels, gene polymorphisms, and autoantigens have all been associated with diabetes risk, the underlying mechanisms remain unknown. Here, we show that DBP regulates α cell morphology, α cell function, and glucagon secretion. Deletion of DBP leads to smaller and hyperplastic α cells, altered Na channel conductance, impaired α cell activation by low glucose, and reduced rates of glucagon secretion both in vivo and in vitro. Mechanistically, this involves reversible changes in islet microfilament abundance and density, as well as changes in glucagon granule distribution. Defects are also seen in β cell and δ cell function. Immunostaining of human pancreata reveals generalized loss of DBP expression as a feature of late-onset and long-standing, but not early-onset, type 1 diabetes. Thus, DBP regulates α cell phenotype, with implications for diabetes pathogenesis.
Topics: Animals; Biological Transport; Bodily Secretions; Cell Communication; Glucagon; Glucagon-Secreting Cells; Humans; Mice, Knockout; Phenotype; Vitamin D; Vitamin D-Binding Protein
PubMed: 32553153
DOI: 10.1016/j.celrep.2020.107761 -
Science Signaling Aug 2020The oral bacterium is often found in colorectal cancer (CRC). In the 21 July 2020 issue of , Casasanta show that CRC cell-resident promotes cytokine secretion that... (Review)
Review
The oral bacterium is often found in colorectal cancer (CRC). In the 21 July 2020 issue of , Casasanta show that CRC cell-resident promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients.
Topics: Bodily Secretions; Cell Movement; Chemokine CXCL1; Colorectal Neoplasms; Fusobacterium nucleatum; Humans; Interleukin-8
PubMed: 32788340
DOI: 10.1126/scisignal.abc4218 -
BMC Microbiology Oct 2013Coxiella burnetii is a Gram-negative intracellular bacterial pathogen that replicates within a phagolysosome-like parasitophorous vacuole (PV) of macrophages. PV...
BACKGROUND
Coxiella burnetii is a Gram-negative intracellular bacterial pathogen that replicates within a phagolysosome-like parasitophorous vacuole (PV) of macrophages. PV formation requires delivery of effector proteins directly into the host cell cytoplasm by a type IVB secretion system. However, additional secretion systems are likely responsible for modification of the PV lumen microenvironment that promote pathogen replication.
RESULTS
To assess the potential of C. burnetii to secrete proteins into the PV, we analyzed the protein content of modified acidified citrate cysteine medium for the presence of C. burnetii proteins following axenic (host cell-free) growth. Mass spectrometry generated a list of 105 C. burnetii proteins that could be secreted. Based on bioinformatic analysis, 55 proteins were selected for further study by expressing them in C. burnetii with a C-terminal 3xFLAG-tag. Secretion of 27 proteins by C. burnetii transformants was confirmed by immunoblotting culture supernatants. Tagged proteins expressed by C. burnetii transformants were also found in the soluble fraction of infected Vero cells, indicating secretion occurs ex vivo. All secreted proteins contained a signal sequence, and deletion of this sequence from selected proteins abolished secretion. These data indicate protein secretion initially requires translocation across the inner-membrane into the periplasm via the activity of the Sec translocase.
CONCLUSIONS
C. burnetii secretes multiple proteins, in vitro and ex vivo, in a Sec-dependent manner. Possible roles for secreted proteins and secretion mechanisms are discussed.
Topics: Animals; Bacterial Proteins; Chlorocebus aethiops; Computational Biology; Coxiella burnetii; Culture Media; Mass Spectrometry; Metabolic Networks and Pathways; Mutant Proteins; Protein Sorting Signals; Protein Transport; Sequence Deletion; Vero Cells
PubMed: 24093460
DOI: 10.1186/1471-2180-13-222 -
International Journal of Molecular... Dec 2023Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release... (Review)
Review
Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release and secrete effector proteins to acquire nutrients and compete with other microorganisms for living space during long-term evolution. Consequently, bacteria have developed a range of secretion systems, which are complex macromolecular transport machines responsible for transporting proteins across the bacterial cell membranes. Among them, one particular secretion system that stands out from the rest is the type V secretion system (T5SS), known as the "autotransporter". Bacterial activities mediated by T5SS include adherence to host cells or the extracellular matrix, invasion of host cells, immune evasion and serum resistance, contact-dependent growth inhibition, cytotoxicity, intracellular flow, protease activity, autoaggregation, and biofilm formation. In a bacterial body, it is not enough to rely on T5SS alone; in most cases, T5SS cooperates with other secretion systems to carry out bacterial life activities, but regardless of how good the relationship is, there is friction between the secretion systems. T5SS and T1SS/T2SS/T3SS/T6SS all play a synergistic role in the pathogenic processes of bacteria, such as nutrient acquisition, pathogenicity enhancement, and immune modulation, but T5SS indirectly inhibits the function of T4SS. This could be considered a love-hate relationship between secretion systems. This paper uses the systematic literature review methodology to review 117 journal articles published within the period from 1995 to 2024, which are all available from the PubMed, Web of Science, and Scopus databases and aim to elucidate the link between T5SS and other secretion systems, providing clues for future prevention and control of bacterial diseases.
Topics: Type V Secretion Systems; Bacteria; Bodily Secretions; Cell Aggregation; Cell Membrane
PubMed: 38203452
DOI: 10.3390/ijms25010281 -
International Archives of Allergy and... 2020Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation.
INTRODUCTION
Charcot-Leyden crystal (CLC) protein has been regarded as a hallmark of eosinophilic inflammation.
OBJECTIVE
The purpose of this study was to investigate the role and levels of CLC protein in patients with nonallergic rhinitis with eosinophilia syndrome (NARES).
METHODS
Overall, 39 NARES patients and 19 controls were recruited. The severity of nasal symptoms was measured by visual analogue scale and serum and local specific immunoglobulin E were determined in all patients. Nasal eosinophilia was assessed by semiquantitative analysis of eosinophils in nasal scrapings. Nasal secretion CLC protein concentrations were evaluated by ELISA.
RESULTS
CLC protein concentrations were significantly higher in NARES patients than in controls (p < 0.0001). Nasal secretion CLC protein levels were significantly correlated with the degree of eosinophilia in nasal scrapings (rs = 0.331; p = 0.04) in NARES patients. Patients with high CLC protein concentrations displayed more severe nasal symptoms than patients with low CLC protein concentrations (p = 0.0080), particularly, nasal itching (p = 0.0029). Pilot study in 8 NARES patients demonstrated that treatment for 1 month with intranasal fluticasone propionate significantly decreased the nasal secretion CLC protein concentrations from baseline levels (p = 0.0335) and markedly attenuated the degree of swelling of inferior turbinate.
CONCLUSIONS
CLC protein levels are significantly higher in nasal secretions of NARES patients and associated with the degree of nasal eosinophilia and the severity of nasal symptoms. Significantly, nasal secretion CLC protein levels obviously decreased after treatment with intranasal corticosteroids, suggesting its possible role in evaluating the medical treatment.
Topics: Adult; Bodily Secretions; Disease Progression; Eosinophilia; Female; Glycoproteins; Humans; Immunoglobulin E; Lysophospholipase; Male; Middle Aged; Nasal Mucosa; Rhinitis; Syndrome; Up-Regulation; Young Adult
PubMed: 32694242
DOI: 10.1159/000509252 -
Scientific Reports Apr 2018Trimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO...
Trimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO uptake into renal proximal tubular cells. Here we investigated the potential role of multidrug and toxin extrusion protein 1 (MATE1) for translocation of TMAO across the luminal membrane of proximal tubular cells. HEK293 cells stably expressing OCT2 (HEK-OCT2) or MATE1 (HEK-MATE1) were used for uptake studies. Transcellular transport of TMAO was investigated using monolayers of MDCK control cells (MDCK-Co) as well as single- (MDCK-OCT2, MDCK-MATE1) and double-transfected cells (MDCK-OCT2-MATE1). In line with previous studies, HEK-OCT2 cells revealed a 2.4-fold uptake of TMAO compared to control cells (p < 0.001), whereas no significant uptake was observed in HEK-MATE1. In monolayers of MDCK cells, polarised TMAO transcellular transport was not significantly different between MDCK-Co and MDCK-OCT2 cells, but significantly increased in MDCK-MATE1 (p < 0.05) and MDCK-OCT2-MATE1 cells (p < 0.001). The OCT/MATE inhibitor trimethoprim abolished TMAO translocation in MDCK-OCT2-MATE1 cells (p < 0.05). The present data suggest that MATE1 contributes to renal elimination of TMAO. For selected MATE substrates, such as TMAO, uptake studies using non-polarised MATE-expressing cells can reveal false negative results compared to studies using polarised monolayers.
Topics: Animals; Bodily Secretions; Dogs; HEK293 Cells; Humans; Madin Darby Canine Kidney Cells; Methylamines; Organic Cation Transport Proteins; Organic Cation Transporter 2; Oxidants
PubMed: 29704007
DOI: 10.1038/s41598-018-25139-8 -
British Dental Journal Apr 1992The secretions of the major and minor salivary glands, together with the gingival crevicular fluid, constitute the oral fluid or whole saliva which provides the chemical... (Review)
Review
The secretions of the major and minor salivary glands, together with the gingival crevicular fluid, constitute the oral fluid or whole saliva which provides the chemical milieu of the teeth and oral soft tissues. The crucial role of saliva in the maintenance of dental health is demonstrated by the morbidity associated with loss of salivary gland function. In this article, the physiology of the secretory process, the reflex control of whole saliva flow rate, the composition of the fluid, the factors affecting its composition, and the functions of the organic and inorganic components are described. Finally, the clinical aspects of salivary gland dysfunction are briefly discussed.
Topics: Humans; Saliva; Salivary Proteins and Peptides; Secretory Rate
PubMed: 1591115
DOI: 10.1038/sj.bdj.4807861 -
Biochemical and Biophysical Research... Jun 2020Secretion of PDI from platelets and endothelial cells is an important step of all thrombotic events. In the absence of extracellular PDI thrombus formation and fibrin...
Secretion of PDI from platelets and endothelial cells is an important step of all thrombotic events. In the absence of extracellular PDI thrombus formation and fibrin generation may be impaired. Thrombin-mediated PDI secretion is regulated by the stimulation of P2Y receptors. This paper provides evidences that P2Y antagonists or AR agonists may modulate release of PDI molecules from platelets and with less efficiency from endothelial cells. Moreover P2Y antagonization or AR agonization modulates platelet-endothelial interaction. We prove that combinations of P2Y antagonists and AR agonists inhibit platelet-dependent adhesion of cancer cells to endothelium and attenuate cancer cell invasiveness, but longer exposition to AR agonists may stimulate migration of invasive breast cancer cells through endothelium thus leading to increased metastasis.
Topics: Androgen Receptor Antagonists; Blood Platelets; Blood Specimen Collection; Bodily Secretions; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Endothelial Cells; Endothelium; Female; Fibrin; Humans; Neoplasm Metastasis; Platelet Adhesiveness; Protein Disulfide-Isomerases; Purinergic P2Y Receptor Antagonists; Receptors, Androgen; Receptors, Purinergic P2Y12; Signal Transduction; Sulfhydryl Compounds; Thrombin; Thrombosis
PubMed: 32265027
DOI: 10.1016/j.bbrc.2020.03.143 -
Nature Chemistry Sep 2022The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human...
The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity. Our capture molecule for amyloid precipitation (CAP-1) consists of a derivative of Pittsburgh Compound B (dimer) to target the cross β-sheets of amyloids and a biotin moiety for surface immobilization. By coupling CAP-1 to magnetic beads, we demonstrate that we can target the amyloid structure of all protein aggregates present in human cerebrospinal fluid, isolate them for analysis and then characterize them using single-molecule fluorescence imaging and mass spectrometry. Amyloid precipitation enables unbiased determination of the molecular composition and structural features of the in vivo aggregates formed in neurodegenerative diseases.
Topics: Amyloid; Amyloid beta-Peptides; Bodily Secretions; Humans; Protein Aggregates
PubMed: 35798951
DOI: 10.1038/s41557-022-00976-3