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Pflugers Archiv : European Journal of... Apr 2024The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid... (Review)
Review
The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid movement in the gut. Since the first description of "active" transport of HCO ions against a concentration gradient in the 1970s, the fundamental role of HCO transport for multiple intestinal functions has been recognized. The ion transport proteins have been identified and molecularly characterized, and knockout mouse models have given insight into their individual role in a variety of functions. This review describes the progress made in the last decade regarding novel techniques and new findings in the molecular regulation of intestinal HCO transport in the different segments of the gut. We discuss human diseases with defects in intestinal HCO secretion and potential treatment strategies to increase luminal alkalinity. In the last part of the review, the cellular and organismal mechanisms for acid/base sensing in the intestinal tract are highlighted.
Topics: Animals; Mice; Humans; Bicarbonates; Ion Transport; Enterocytes; Cell Membrane; Bodily Secretions; Hydrogen-Ion Concentration; Cystic Fibrosis Transmembrane Conductance Regulator
PubMed: 38374228
DOI: 10.1007/s00424-024-02914-3 -
Current Opinion in Microbiology Jun 2005Many secondary metabolites (e.g. antibiotics and mycotoxins) are toxic to the microorganisms that produce them. The clusters of genes that are responsible for the... (Review)
Review
Many secondary metabolites (e.g. antibiotics and mycotoxins) are toxic to the microorganisms that produce them. The clusters of genes that are responsible for the biosynthesis of secondary metabolites frequently contain genes for resistance to these toxic metabolites, such as different types of multiple drug resistance systems, to avoid suicide of the producer strains. Recently there has been research into the efflux systems of secondary metabolites in bacteria and in filamentous fungi, such as the large number of ATP-binding cassette transporters found in antibiotic-producing Streptomyces species and that are involved in penicillin secretion in Penicillium chrysogenum. A different group of efflux systems, the major facilitator superfamily exporters, occur very frequently in a variety of bacteria that produce pigments or antibiotics (e.g. the cephamycin and thienamycin producers) and in filamentous fungi that produce mycotoxins. Such efflux systems include the CefT exporters that mediate cephalosporin secretion in Acremonium chrysogenum. The evolutionary origin of these efflux systems and their relationship with current resistance determinants in pathogenic bacteria has been analyzed. Genetic improvement of the secretion systems of secondary metabolites in the producer strain has important industrial applications.
Topics: Acremonium; Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Bodily Secretions; Carrier Proteins; Fungal Proteins; Molecular Sequence Data; Streptomyces
PubMed: 15939351
DOI: 10.1016/j.mib.2005.04.009 -
International Review of Cytology 2004Exocytosis is an essential membrane traffic event mediating the secretion of intracellular protein contents such as hormones and neurotransmitters as well as the... (Review)
Review
Exocytosis is an essential membrane traffic event mediating the secretion of intracellular protein contents such as hormones and neurotransmitters as well as the incorporation of membrane proteins and lipids to specific domains of the plasma membrane. As a fundamental cell biological process, exocytosis is crucial for cell growth, cell-cell communication, and cell polarity establishment. For most eukaryotic cells exocytosis is polarized. A multiprotein complex, named the exocyst, is required for polarized exocytosis from yeast to mammals. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84. They are localized to sites of active exocytosis, where they mediate the targeting and tethering of post-Golgi secretory vesicles for subsequent membrane fusion. Here we review the progress made in the understanding of the exocyst and its role in polarized exocytosis.
Topics: Animals; Bodily Secretions; Cell Membrane; Cell Polarity; Exocytosis; Humans; Macromolecular Substances; Membrane Fusion; Multiprotein Complexes; Protein Transport; Saccharomyces cerevisiae Proteins; Secretory Vesicles
PubMed: 15037366
DOI: 10.1016/S0074-7696(04)33006-8 -
The Journal of Cell Biology Aug 2002Pathogenic Yersinia spp (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) have evolved an exquisite method for delivering powerful effectors... (Review)
Review
Pathogenic Yersinia spp (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) have evolved an exquisite method for delivering powerful effectors into cells of the host immune system where they inhibit signaling cascades and block the cells' response to infection. Understanding the molecular mechanisms of this system has provided insight into the processes of phagocytosis and inflammation.
Topics: Adhesins, Bacterial; Animals; Bodily Secretions; Cell Surface Extensions; Eukaryotic Cells; Humans; Inflammation; Phagocytosis; Protein Transport; Yersinia; Yersinia Infections
PubMed: 12163464
DOI: 10.1083/jcb.200205077 -
International Journal of Molecular... Dec 2021Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the...
Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca] increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca] induced by the activation of H1, H3, or H4 receptors, whereas RvD1 inhibited H1 and H3 receptors. RvD2 and RvD1 also activate distinct receptor-specific protein kinases to counter-regulate the histamine receptors, probably by phosphorylation. Thus, our data suggest that the counter-regulation of H receptor subtypes by RvD2 and RvD1 to inhibit mucin secretion are separately regulated.
Topics: Animals; Bodily Secretions; Calcium; Cells, Cultured; Conjunctiva; Docosahexaenoic Acids; Female; Goblet Cells; Histamine; Humans; Male; Mucins; Protein Kinases; Rats; Rats, Sprague-Dawley
PubMed: 35008563
DOI: 10.3390/ijms23010141 -
Methods in Molecular Biology (Clifton,... 2024Infection experiments with Galleria mellonella enable the measurement of virulence that is mediated by secretion systems and their effector proteins in vivo. G....
Infection experiments with Galleria mellonella enable the measurement of virulence that is mediated by secretion systems and their effector proteins in vivo. G. mellonella has an innate immune system and shares similarities with the complex host environment of mammals. Unlike other invertebrate model systems, experiments can be performed at mammalian body temperature. Here, we describe the systemic infection of G. mellonella with Pseudomonas aeruginosa with and without functional secretion systems. A Kaplan-Meier curve is constructed showing the percent survival of animals over time.
Topics: Animals; Bodily Secretions; Body Temperature; Models, Biological; Pseudomonas aeruginosa; Sepsis; Mammals
PubMed: 37930555
DOI: 10.1007/978-1-0716-3445-5_38 -
Clinical Neuropathology 2020Only a few cases of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the setting of amyotrophic lateral sclerosis (ALS) have been described in the... (Review)
Review
Only a few cases of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the setting of amyotrophic lateral sclerosis (ALS) have been described in the literature. We present the case of an 81-year-old male who developed severe hyponatremia following elective total hip replacement. His past medical history included prostate cancer, which was under surveillance, and ischemic heart disease. He reported recent weight loss, worsening shortness of breath, and lethargy. SIADH was diagnosed on the basis of hyponatremia, elevated urinary sodium, and decreased serum osmolality, presumed secondary to surgery. Investigations revealed no occult malignancy and no other cause for hyponatremia. He was discharged when sodium levels had normalized, however, he then had several further admissions for hyponatremia, general fatigue, and breathlessness. His condition continued to decline, and he developed dysphagia, weakness, and tongue fasciculations. Neurological examination showed globally decreased power, increased tone, and fasciculations. MRI of the brain was normal. He did not respond to neostigmine treatment, and a presumed diagnosis of motor neuron disease was made. The patient passed away shortly after this, and a post-mortem confirmed the diagnosis of ALS. Drug, post-operative, and cancer-related causes were precluded by the timing of onset of hyponatremia. We present this case and an analysis of previously published cases alongside a discussion on the potential causative mechanisms.
Topics: Aged, 80 and over; Amyotrophic Lateral Sclerosis; Bodily Secretions; Brain; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Vasopressins
PubMed: 32449677
DOI: 10.5414/NP301280 -
Nature Communications Feb 2021
Topics: Bodily Secretions; Extracellular Vesicles; Receptors, Endothelin; Sulfisoxazole
PubMed: 33579909
DOI: 10.1038/s41467-021-21074-x -
Cells Jan 2024MRGPRX2, the human member of the MAS-related G-protein-coupled receptors (GPCRs), mediates the immunoglobulin E (IgE)-independent responses of a subset of mast cells...
MRGPRX2, the human member of the MAS-related G-protein-coupled receptors (GPCRs), mediates the immunoglobulin E (IgE)-independent responses of a subset of mast cells (MCs) that are associated with itch, pain, neurogenic inflammation, and pseudoallergy to drugs. The mechanisms underlying the responses of MRGPRX2 to its multiple and diverse ligands are still not completely understood. Given the close association between GPCR location and function, and the key role played by Rab GTPases in controlling discrete steps along vesicular trafficking, we aimed to reveal the vesicular pathways that directly impact MRGPRX2-mediated exocytosis by identifying the Rabs that influence this process. For this purpose, we screened 43 Rabs for their functional and phenotypic impacts on MC degranulation in response to the synthetic MRGPRX2 ligand compound 48/80 (c48/80), which is often used as the gold standard of MRGPRX2 ligands, or to substance P (SP), an important trigger of neuroinflammatory MC responses. Results of this study highlight the important roles played by macropinocytosis and autophagy in controlling MRGPRX2-mediated exocytosis, demonstrating a close feedback control between the internalization and post-endocytic trafficking of MRGPRX2 and its triggered exocytosis.
Topics: Humans; Bodily Secretions; Exocytosis; Autophagy; Immunoglobulin E; Inflammation; Secretory Vesicles; Nerve Tissue Proteins; Receptors, Neuropeptide; Receptors, G-Protein-Coupled
PubMed: 38201297
DOI: 10.3390/cells13010093 -
Gastroenterology Oct 2003A secretion-incompetent, highly replicating hepatitis B variant was previously found as the dominant viral population in the serum of a liver transplant recipient with...
BACKGROUND AND AIMS
A secretion-incompetent, highly replicating hepatitis B variant was previously found as the dominant viral population in the serum of a liver transplant recipient with severe hepatitis B reinfection. The secretion block resulted from mutations in the S protein, including the Gly145Arg substitution known to emerge under antibody to hepatitis B surface antigen immunoglobulin treatment. Here we investigated the mechanisms that allow selection of a secretion-incompetent virus as the predominant strain in the serum.
METHODS
To reproduce the interaction of viral quasispecies occurring in vivo, cotransfection experiments were performed with full-length genomes containing wild-type or mutant sequences. In addition, the relevance of mutations in the common S part of the surface proteins for the competence of L and S protein to support viral secretion was studied.
RESULTS
A small amount of wild-type virus or of a wild-type S protein-expressing variant rescued secretion of the defective mutant. In the secreted virions, the high-replicating mutant genome was predominant. Selection of the defective mutant was further supported by a transdominant negative effect of mutant S protein on wild-type virion secretion. In contrast, mutant L protein with the same c-terminal mutations as mutant S protein efficiently supported virion formation and secretion.
CONCLUSIONS
Interaction of the variant with a small amount of wild-type virus can reverse its secretion-defective phenotype. Mutations in the common region of S and L protein have different consequences for the ability of the envelope proteins to support virion assembly and secretion.
Topics: Bodily Secretions; Gene Expression Regulation, Viral; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Phenotype; Viral Envelope Proteins; Virion; Virus Replication
PubMed: 14517791
DOI: 10.1016/s0016-5085(03)01202-2