scholarly journals Scavenger receptors in host defense: from functional aspects to mode of action

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Qamar Taban ◽  
Peerzada Tajamul Mumtaz ◽  
Khalid Z. Masoodi ◽  
Ehtishamul Haq ◽  
Syed Mudasir Ahmad
Keyword(s):  
Mode Of Action ◽  
Microbial Pathogens ◽  
Soluble Form ◽  
Scavenger Receptors ◽  
Angiotensin Converting Enzyme 2 ◽  
Major Function ◽  
Functional Aspects ◽  
Membrane Bound ◽  
Pathogen Entry ◽  
Functionally Diverse

AbstractScavenger receptors belong to a superfamily of proteins that are structurally heterogeneous and encompass the miscellaneous group of transmembrane proteins and soluble secretory extracellular domain. They are functionally diverse as they are involved in various disorders and biological pathways and their major function in innate immunity and homeostasis. Numerous scavenger receptors have been discovered so far and are apportioned in various classes (A-L). Scavenger receptors are documented as pattern recognition receptors and known to act in coordination with other co-receptors such as Toll-like receptors in generating the immune responses against a repertoire of ligands such as microbial pathogens, non-self, intracellular and modified self-molecules through various diverse mechanisms like adhesion, endocytosis and phagocytosis etc. Unlike, most of the scavenger receptors discussed below have both membrane and soluble forms that participate in scavenging; the role of a potential scavenging receptor Angiotensin-Converting Enzyme-2 has also been discussed whereby only its soluble form might participate in preventing the pathogen entry and replication, unlike its membrane-bound form. This review majorly gives an insight on the functional aspect of scavenger receptors in host defence and describes their mode of action extensively in various immune pathways involved with each receptor type.

Antimicrobial Peptides - Small but Mighty Weapons for Plants to Fight Phytopathogens

2019 ◽  
Vol 26 (10) ◽  
pp. 720-742 ◽  
Author(s):  
Kaushik Das ◽  
Karabi Datta ◽  
Subhasis Karmakar ◽  
Swapan K. Datta
Keyword(s):  
Antimicrobial Peptides ◽  
Durable Resistance ◽  
Defense Responses ◽  
Defense System ◽  
Biotechnological Potential ◽  
Functional Aspects ◽  
Low Concentrations ◽  
Wide Range ◽  
Vital Component ◽  
Pathogen Entry

Antimicrobial Peptides (AMPs) have diverse structures, varied modes of actions, and can inhibit the growth of a wide range of pathogens at low concentrations. Plants are constantly under attack by a wide range of phytopathogens causing massive yield losses worldwide. To combat these pathogens, nature has armed plants with a battery of defense responses including Antimicrobial Peptides (AMPs). These peptides form a vital component of the two-tier plant defense system. They are constitutively expressed as part of the pre-existing first line of defense against pathogen entry. When a pathogen overcomes this barrier, it faces the inducible defense system, which responds to specific molecular or effector patterns by launching an arsenal of defense responses including the production of AMPs. This review emphasizes the structural and functional aspects of different plant-derived AMPs, their homology with AMPs from other organisms, and how their biotechnological potential could generate durable resistance in a wide range of crops against different classes of phytopathogens in an environmentally friendly way without phenotypic cost.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

Soluble neutral maltase–glucoamylase from the small intestine: separation and characterization of components with differing affinity for concanavalin A

1982 ◽  
Vol 60 (11) ◽  
pp. 1007-1013 ◽  
Author(s):  
G. Forstner ◽  
A. Salvatore ◽  
L. Lee ◽  
J. Forstner
Keyword(s):  
Concanavalin A ◽  
Gradient Elution ◽  
Soluble Form ◽  
Rat Intestine ◽  
Ph Optimum ◽  
Molecular Weights ◽  
Neutral Ph ◽  
Membrane Bound ◽  
Sepharose 4B

Intestinal maltase with a neutral pH optimum exists in both a brush border membrane-bound form and a soluble form in suckling rat intestine. Previous experiments in our laboratory have shown that the soluble enzyme contains a component which binds much more tightly to concanavalin A (ConA) than solubilized forms of the membrane enzyme. We studied the origin of this component by subjecting neutral, soluble maltase activity to chromatography on Sepharose 4B at age 13, 18 (preweaning), and 25 (postweaning) days. At 13 days, two maltase peaks were obtained with approximate molecular weights of 400 000 (peak I) and 150 000 (peak II). Peak II was less prominent at 18 days and was absent at 25 days. At 13 days, the majority of peak I consisted of material which was bound between 0.025 and 0.05 M α-methyl mannoside on gradient elution chromatography of ConA-Sepharose. Peak II contained material which eluted between 0.075 and 0.3 M α-methyl mannoside. At 25 days, all of the soluble maltase eluted between 0.025 and 0.04 M α-methyl mannoside. Peak I and peak II maltases had similar pH optima and Km's for maltase. Peak II maltase had a fourfold greater activity toward glycogen than peak I maltase with approximately the same activity for palatinose, turanose, and trehalose. Both maltases were precipitated by an antibody raised against adult membrane-bound maltase. Soluble maltase with neutral pH activity in the suckling rat intestine, therefore, consists of two immunologically related isozymes which differ in their molecular weight, their binding by ConA, and their specificity for glycogen. The small isozyme disappears at or about the time of weaning.

scholarly journals Characterization of the soluble, secreted form of urinary meprin

1996 ◽  
Vol 315 (2) ◽  
pp. 461-465 ◽  
Author(s):  
Robert J. BEYNON ◽  
Simon OLIVER ◽  
Duncan H. L. ROBERTSON
Keyword(s):  
Proteolytic Activity ◽  
Protein Band ◽  
Peptide Sequence ◽  
Soluble Form ◽  
Α Subunit ◽  
Alternative Processing ◽  
Sds Page ◽  
Processing Pathways ◽  
Membrane Bound

A soluble form of the kidney membrane metalloendopeptidase, meprin, is present in urine. Urinary meprin is expressed in BALB/C mice with the Mep-1a/a genotype (high meprin, expressing meprin-α and meprin-β) but not in BALB.K mice of the Mep-1b/b genotype (that only express meprin-β). Western blotting with antisera specific to the meprin-α and the meprin-β subunits established that the only form of meprin present in urine samples was derived from meprin-α. This form of meprin is partially active, and comprises at least three variants by non-reducing SDS/PAGE and by zymography and two protein bands on reducing SDS/PAGE. Sequencing of these two bands established that the N-terminus of the larger protein band begins with the pro-peptide sequence of the α-subunit (VSIKH..), whereas the smaller band possessed the mature meprin N-terminal sequence (NAMRDP..). Trypsin is able to remove the pro-peptide, with a concomitant activation in proteolytic activity. After deglycosylation, the size of the pro- and mature forms of urinary meprin are consistent with cleavage in the region of the X–I boundary. There is a pronounced sexual dimorphism in urinary meprin expression. Females secrete a slightly larger form, and its proteolytic activity is about 50% of that released by males. The urinary meprin is therefore a naturally occurring secreted form of this membrane-bound metalloendopeptidase and is more likely to be generated by alternative processing pathways than by specific release mechanisms.

scholarly journals Role of glycosylation in transport and enzymic activity of neutral endopeptidase-24.11

1994 ◽  
Vol 302 (2) ◽  
pp. 451-454 ◽  
Author(s):  
M H Lafrance ◽  
C Vézina ◽  
Q Wang ◽  
G Boileau ◽  
P Crine ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cell Surface ◽  
Intracellular Transport ◽  
Neutral Endopeptidase ◽  
Soluble Form ◽  
Cell Extracts ◽  
Glycosylation Sites ◽  
Sugar Addition ◽  
Membrane Bound

Neutral endopeptidase (NEP, EC 3.4.24.11) is a major ectoenzyme of the brush-border membrane. The ectodomain of NEP contains five putative N-glycosylation sites. In order to determine the role of the addition of sugar moieties on the activity and intracellular transport of NEP, we have used site-directed mutagenesis to remove all or some of the five potential sites of sugar addition in membrane-bound and secreted forms of the enzyme. Expression of NEP glycosylation mutants in COS-1 cells showed that all five sites are used for sugar addition. Immunoblotting of NEP in COS-1 cell extracts or culture media indicated that total expression of normal membrane-bound NEP was not affected by mutations at glycosylation sites, whereas this expression level appeared to be strictly dependent on the number of glycosylation sites retained on the soluble form. The transport to the cell surface was also reduced by decreased glycosylation, but again the phenomenon appeared more drastic in the case of the soluble form than for the membrane-bound enzyme. Enzyme activity was decreased by deglycosylation. However, the presence of either of two crucial sites (sites 1 and 5; numbered from the N-terminus of the protein) was sufficient to recover close-to-normal enzymic activities. Transport to the cell surface and enzyme activity of NEP are thus both dependent on sugar residues, probably through different conformational constraints. These constraints seem to be local for enzyme activity but more global for transport to the cell surface.

scholarly journals Effects of Carboxypeptidase E Overexpression on Insulin mRNA Levels, Regulated Insulin Secretion, and Proinsulin Processing of Pituitary GH3 Cells Transfected with a Furin-Cleavable Human Proinsulin cDNA

2002 ◽  
Vol 11 (8) ◽  
pp. 803-811 ◽  
Author(s):  
Luca Polastri ◽  
Francesca Galbiati ◽  
Franco Folli ◽  
Alberto M. Davalli
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Secretory Granules ◽  
Gh3 Cells ◽  
Soluble Form ◽  
Mrna Levels ◽  
Carboxypeptidase E ◽  
Proinsulin Processing ◽  
Membrane Bound ◽  
Overexpressing Cell

We recently developed two rat pituitary GH3 cell clones engineered to secrete human insulin (InsGH3). InsGH3 cells convert proinsulin into mature insulin, which is partially stored into a readily releasable pool of secretory granules. The efficiency of these processes, however, is relatively low in these cells, either in vitro or in vivo. This study was aimed at determining whether carboxypeptidase E (Cpe) overexpression can increase proinsulin processing and regulated secretion by InsGH3 clones. Indeed, in its membrane-bound form Cpe works as sorting receptor for the regulated secretory pathway of many hormones while, in its soluble form, Cpe takes part to the late step of insulin maturation. We obtained two Cpe-overexpressing cell lines from two different InsGH3 clones (InsGH3/C1 and C7). In the Cpe-overexpressing cell lines, derived from InsGH3 of clone 1 (InsGH3/C1-HACpe), in which the membrane-bound form of exogenous Cpe is accounted for by 90% of total Cpe immunoreactivity, we observed an increase in proinsulin gene expression, and in basal and stimulated insulin secretion compared with the original clone. In contrast, in the Cpe-overexpressing cell line derived from InsGH3 of clone 7 (InsGH3/C7-HACpe), where the exogenous membrane-bound form was only 60% of total Cpe, we detected a decrease in basal insulin release and a modest, albeit significant, increase in intracellular proinsulin processing. In conclusion, Cpe overexpression can increase regulated insulin secretion and proinsulin processing in InsGH3 cells; however, such improvements appear quantitatively and qualitatively modest.

scholarly journals The membrane-bound and soluble form of melanotransferrin function independently in the diagnosis and targeted therapy of lung cancer

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Yuanyuan Lei ◽  
Zhiliang Lu ◽  
Jianbing Huang ◽  
Ruochuan Zang ◽  
Yun Che ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Cells ◽  
Tumor Staging ◽  
Soluble Form ◽  
Advanced Lung Cancer ◽  
Autologous Tumor ◽  
Vascular Endothelial ◽  
The Public ◽  
Common Marker ◽  
Membrane Bound

Abstract Melanotransferrin (MFI2) is a newly identified tumor-associated protein, which consists of two forms of proteins, membrane-bound (mMFI2) and secretory (sMFI2). However, little is known about the expression pattern and their relevance in lung cancer. Here, we found that both two forms of MFI2 are highly expressed in lung cancer. The expression of MFI2 in lung cancer was detected by using the public database and qRT-PCR. Overexpression and knockdown cell lines and recombinant sMFI2 protein were used to study the function of mMFI2 and sMFI2. RNA-seq, protein chip, ChIP assay, Immunoprecipitation, ELISA, and immunofluorescence were used to study the molecular biological mechanism of mMFI2 and sMFI2. We found that mMFI2 promoted the expression of EMT’s common marker N-cadherin by downregulating the transcription factor KLI4, which in turn promoted tumor metastasis; sMFI2 could promote the metastasis of autologous tumor cells in an autocrine manner but the mechanism is different from that of mMFI2. In addition, sMFI2 was proved could inhibit the migration of vascular endothelial cells and subsequently enhance angiogenic responses in a paracrine manner. We propose that the expressions and functions of the two forms of MFI2 in lung cancer are relatively independent. Specifically, mMFI2 was a potential lung cancer therapeutic target, while sMFI2 was highly enriched in advanced lung cancer, and could be used as a tumor staging index.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 641-649 ◽  
Author(s):  
K Miyazawa ◽  
DA Williams ◽  
A Gotoh ◽  
J Nishimaki ◽  
HE Broxmeyer ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tyrosine Kinase ◽  
Life Span ◽  
Protein Degradation ◽  
Cell Line ◽  
Soluble Form ◽  
Steel Factor ◽  
Degradation Rates ◽  
Membrane Bound ◽  
Kinetics Of

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4- h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4- h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a “turn-off switch” for activated c-kit kinase.

scholarly journals Biosynthesis of intestinal microvillar proteins. Pulse-chase labelling studies on maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV

1983 ◽  
Vol 210 (2) ◽  
pp. 389-393 ◽  
Author(s):  
E M Danielsen ◽  
H Sjöström ◽  
O Norén
Keyword(s):  
Organ Culture ◽  
Membrane Fraction ◽  
Bound State ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Soluble Form ◽  
Membrane Bound ◽  
Aminopeptidase A ◽  
High Mannose ◽  
Small Intestinal

The biogenesis of three intestinal microvillar enzymes, maltase-glucoamylase (EC 3.2.1.20), aminopeptidase A (aspartate aminopeptidase, EC 3.4.11.7) and dipeptidyl peptidase IV (EC 3.4.14.5), was studied by pulse-chase labelling of pig small-intestinal explants kept in organ culture. The earliest detectable forms of the enzymes were polypeptides of Mr 225000, 140000 and 115000 respectively. These were found to represent the enzymes in a ‘high-mannose’ state of glycosylation, as judged by their susceptibility to treatment with endo-beta-N-acetylglucosaminidase H (EC 3.2.1.96). After about 40-60 min of chase, maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV were further modified to yield the mature polypeptides of Mr 245000, 170000 and 137000 respectively, which were expressed at the microvillar membrane after 60-90 min of chase. The fact that the enzymes before reaching the microvillar membrane were found in a Ca2+-precipitated membrane fraction (intracellular and basolateral membranes), but not in soluble form, indicates that during biogenesis maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV are transported and assembled in a membrane-bound state.

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