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Endocrine Reviews Jun 2020The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need... (Review)
Review
The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.
Topics: Adrenocorticotropic Hormone; Animals; Bodily Secretions; Circadian Rhythm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Secretory Pathway
PubMed: 32060528
DOI: 10.1210/endrev/bnaa002 -
Nature Immunology May 2017The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease...
The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions. By integrating total and secreted proteomes, we discovered fundamental intercellular communication structures and previously unknown connections between cell types. Our publicly accessible (http://www.immprot.org/) proteomic resource provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.
Topics: Animals; Blood Cells; Bodily Secretions; Cell Communication; Computer Simulation; Humans; Immunity, Cellular; Mass Spectrometry; Protein Interaction Maps; Proteome; Proteomics; Social Support
PubMed: 28263321
DOI: 10.1038/ni.3693 -
Methods in Molecular Biology (Clifton,... 2021The analysis of eosinophil shape change and mediator secretion is a useful tool in understanding how eosinophils respond to immunological stimuli and chemotactic...
The analysis of eosinophil shape change and mediator secretion is a useful tool in understanding how eosinophils respond to immunological stimuli and chemotactic factors. Eosinophils undergo dramatic shape changes, along with secretion of the granule-derived enzyme eosinophil peroxidase (EPX) in response to chemotactic stimuli including platelet-activating factor (PAF) and CCL11 (eotaxin-1). Here, we describe the analysis of eosinophil shape change by confocal microscopy analysis and provide an experimental approach for comparing unstimulated cells with those that have been stimulated to undergo chemotaxis. In addition, we illustrate two different degranulation assays for EPX using OPD and an ELISA technique and show how eosinophil degranulation may be assessed from in vitro as well as ex vivo stimulation.
Topics: Bodily Secretions; Cell Degranulation; Cell Shape; Chemokine CCL11; Chemotaxis; Enzyme-Linked Immunosorbent Assay; Eosinophil Peroxidase; Eosinophils; Humans; Leukocytes; Microscopy, Fluorescence; Neutrophils; Platelet Activating Factor; Secretory Pathway
PubMed: 33486739
DOI: 10.1007/978-1-0716-1095-4_17 -
Nutrients Mar 2021The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the... (Review)
Review
The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile.
Topics: Bodily Secretions; Enteroendocrine Cells; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Gastrointestinal Tract; Glucagon-Like Peptide 1; Humans; Nutritional Physiological Phenomena; Postprandial Period
PubMed: 33803183
DOI: 10.3390/nu13030883 -
Current Opinion in Microbiology Oct 2003Secretion of proteins into the extracellular environment is important to almost all bacteria, and in particular mediates interactions between pathogenic or symbiotic... (Review)
Review
Secretion of proteins into the extracellular environment is important to almost all bacteria, and in particular mediates interactions between pathogenic or symbiotic bacteria with their eukaryotic hosts. The accumulation of bacterial genome sequence data in the past few years has provided great insights into the distribution and function of these secretion systems. Three systems are responsible for secretion of proteins across the bacterial cytoplasmic membrane: Sec, SRP and Tat. Many novel examples of systems for transport across the Gram-negative bacterial cell envelope have been discovered through genome sequencing and surveys, including many novel type III secretion systems and autotransporters. Similarly, genomic data mining has revealed many new potential secretion substrates and identified unsuspected domains in secretion-associated proteins. Interestingly, genomic analyses have also hinted at the existence of a dedicated protein secretion system in Gram-positive bacteria, targeting members of the WXG100/ESAT-6 family of proteins, and have revealed an unexpectedly wide distribution of sortase-driven protein-targeting systems.
Topics: Bacteria; Bodily Secretions; Genomics; Virulence
PubMed: 14572546
DOI: 10.1016/j.mib.2003.09.005 -
Nature Chemical Biology Jan 2006
Topics: Animals; Benzazepines; Binding Sites; Bodily Secretions; Cell Membrane; Galantamine; Guanine Nucleotide Dissociation Inhibitors; Humans; Oximes; cdc42 GTP-Binding Protein; rho GTP-Binding Proteins
PubMed: 16408080
DOI: 10.1038/nchembio0106-7 -
Frontiers in Cellular and Infection... 2019, as a facultative intracellular pathogen, can interact with host macrophages and modulate macrophage function to influence innate and adaptive immunity. Proteins...
, as a facultative intracellular pathogen, can interact with host macrophages and modulate macrophage function to influence innate and adaptive immunity. Proteins secreted by the ESX-1 secretion system are involved in this relationship. Although the importance of ESX-1 in host-pathogen interactions and virulence is well-known, the primary role is ascribed to EsxA (EAST-6) in mycobacterial pathogenesis and the functions of individual components in the interactions between pathogens and macrophages are still unclear. Here, we investigated the effects of EspC on macrophage activation. The EspC protein is encoded by an cluster, which is not linked to the locus, but is essential for the secretion of the major virulence factors of ESX-1, EsxA and EsxB. Our results showed that both EspC protein and EspC overexpression in induced pro-inflammatory cytokines and enhanced surface marker expression. This mechanism was dependent on Toll-like receptor 4 (TLR4), as demonstrated using EspC-treated macrophages from TLR4 mice, leading to decreased pro-inflammatory cytokine secretion and surface marker expression compared with those from wild-type mice. Immunoprecipitation and immunofluorescence assays showed that EspC interacted with TLR4 directly. Moreover, EspC could activate macrophages and promote antigen presentation by inducing mitogen-activated protein kinase (MAPK) phosphorylation and nuclear factor-κB activation. The EspC-induced cytokine expression, surface marker upregulation, and MAPK signaling activation were inhibited when macrophages were blocked with anti-TLR4 antibodies or pretreated with MAPK inhibitors. Furthermore, our results showed that EspC overexpression enhanced the survival of within macrophages and under stress conditions. Taken together, our results indicated that EspC may be another ESX-1 virulence factor that not only modulates the host innate immune response by activating macrophages through TLR4-dependent MAPK signaling but also plays an important role in the survival of pathogenic mycobacteria in host cells.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Bodily Secretions; Cytokines; Host-Pathogen Interactions; Humans; Immunity, Innate; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinases; Mycobacterium tuberculosis; Protein C; RAW 264.7 Cells; Signal Transduction; THP-1 Cells; Toll-Like Receptor 2; Toll-Like Receptor 4; Virulence Factors
PubMed: 31134163
DOI: 10.3389/fcimb.2019.00158 -
Neuroendocrinology 2023Identification of the molecular mechanisms governing neuroendocrine secretion and resulting intercellular communication is one of the great challenges of cell biology to... (Review)
Review
Identification of the molecular mechanisms governing neuroendocrine secretion and resulting intercellular communication is one of the great challenges of cell biology to better understand organism physiology and neurosecretion disruption-related pathologies such as hypertension, neurodegenerative, or metabolic diseases. To visualize molecule distribution and dynamics at the nanoscale, many imaging approaches have been developed and are still emerging. In this review, we provide an overview of the pioneering studies using transmission electron microscopy, atomic force microscopy, total internal reflection microscopy, and super-resolution microscopy in neuroendocrine cells to visualize molecular mechanisms driving neurosecretion processes, including exocytosis and associated fusion pores, endocytosis and associated recycling vesicles, and protein-protein or protein-lipid interactions. Furthermore, the potential and the challenges of these different advanced imaging approaches for application in the study of neuroendocrine cell biology are discussed, aiming to guide researchers to select the best approach for their specific purpose around the crucial but not yet fully understood neurosecretion process.
Topics: Exocytosis; Bodily Secretions; Diagnostic Imaging
PubMed: 34915491
DOI: 10.1159/000521457 -
Bone Research Aug 2023Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of...
Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function in Sost, which models sclerosteosis, and two strains of mice carrying different point mutations in Lrp5 (equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5-6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.
Topics: Animals; Humans; Mice; Adaptor Proteins, Signal Transducing; Bodily Secretions; Disease Models, Animal; Gain of Function Mutation; Hyperostosis; Low Density Lipoprotein Receptor-Related Protein-5; Mutation
PubMed: 37612291
DOI: 10.1038/s41413-023-00278-5 -
Parasites & Vectors Jan 2022Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are... (Review)
Review
Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are intrinsically modulated during developmental transitions, physiological processes and disease progression. Also, proteins are integral components of parasite structural elements and organelles. Among apicomplexan parasites, Eimeria species are an important disease aetiology for economically important animals wherein identification and characterisation of proteins have been long-winded. Nonetheless, this review seeks to give a comprehensive overview of constitutively expressed Eimeria proteins. These molecules are discussed across developmental stages, organelles and sub-cellular components vis-à-vis their biological functions. In addition, hindsight and suggestions are offered with intention to summarise the existing trend of eimerian protein characterisation and to provide a baseline for future studies.
Topics: Animals; Antigens, Protozoan; Apicomplexa; Bodily Secretions; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Genes, Protozoan; Host-Parasite Interactions; Humans; Membrane Proteins; Merozoites; Oocysts; Organelles; Peptide Hydrolases; Poultry Diseases; Protein Transport; Sporozoites
PubMed: 35073987
DOI: 10.1186/s13071-022-05159-0