Bacterial plasminogen receptors: mediators of a multifaceted relationship.
Ontology highlight
ABSTRACT:
SUBMITTER: Sanderson-Smith ML
PROVIDER: S-EPMC3478875 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Bacterial plasminogen receptors: mediators of a multifaceted relationship.
Sanderson-Smith Martina L ML De Oliveira David M P DM Ranson Marie M McArthur Jason D JD
Journal of biomedicine & biotechnology 20121014
Multiple species of bacteria are able to sequester the host zymogen plasminogen to the cell surface. Once localised to the bacterial surface, plasminogen can act as a cofactor in adhesion, or, following activation to plasmin, provide a source of potent proteolytic activity. Numerous bacterial plasminogen receptors have been identified, and the mechanisms by which they interact with plasminogen are diverse. Here we provide an overview of bacterial plasminogen receptors and discuss the diverse rol ...[more]
Similar Datasets
Project description:BACKGROUND:Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the disorder. Based on this hypothesized role for VP in neuropsychiatric disorders, much research is currently being undertaken in humans and animals to test VP as a target for treatment of a number of these disorders including alcohol abuse. OBJECTIVES:To provide a summary of the literature regarding the role of VP in alcohol- and stress-related behaviors including the use of drugs that target VP in clinical trials. RESULTS:Changes in various components of the VP system occur with alcohol and stress. Manipulating VP or its receptors can alter alcohol- and stress-related behaviors including tolerance to alcohol, alcohol drinking, and anxiety-like behavior. Finally, the hypothalamic-pituitary-adrenal axis response to alcohol is also altered by manipulating the VP system. However, clinical trials of VP antagonists have had mixed results. CONCLUSIONS:A review of VP's involvement in alcohol's actions demonstrates that there is much to be learned about brain regions involved in VP-mediated effects on behavior. Thus, future work should focus on elucidating relevant brain regions. By using previous knowledge of the actions of VP and determining the brain regions and/or systems involved in its different behavioral effects, it may be possible to identify a specific receptor subtype target, drug treatment combination, or specific clinical contexts that may point toward a more successful treatment.
| S-EPMC6286152 | biostudies-literature
Project description:Mechanosensing and mechanotransduction are vital processes in mechanobiology and play critical roles in regulating cellular behavior and fate. There is increasing evidence that purinergic P2 receptors, members of the purinergic family, play a crucial role in cellular mechanotransduction. Thus, information on the specific mechanism of P2 receptor-mediated mechanotransduction would be valuable. In this review, we focus on purinergic P2 receptor signaling pathways and describe in detail the interaction of P2 receptors with other mechanosensitive molecules, including transient receptor potential channels, integrins, caveolae-associated proteins and hemichannels. In addition, we review the activation of purinergic P2 receptors and the role of various P2 receptors in the regulation of various pathophysiological processes induced by mechanical stimuli.
| S-EPMC8138185 | biostudies-literature
Project description:The role of plasminogen activator inhibitor-1 (PAI-1) in vein graft (VG) remodeling is undefined. We examined the effect of PAI-1 on VG intimal hyperplasia and tested the hypothesis that PAI-1 regulates VG thrombin activity.VGs from wild-type (WT), Pai1(-/-), and PAI-1-transgenic mice were implanted into WT, Pai1(-/-), or PAI-1-transgenic arteries. VG remodeling was assessed 4 weeks later. Intimal hyperplasia was significantly greater in PAI-1-deficient mice than in WT mice. The proliferative effect of PAI-1 deficiency was retained in vitronectin-deficient mice, suggesting that PAI-1's antiproteolytic function plays a key role in regulating intimal hyperplasia. Thrombin-induced proliferation of PAI-1-deficient venous smooth muscle cells (SMC) was significantly greater than that of WT SMC, and thrombin activity was significantly higher in PAI-1-deficient VGs than in WT VGs. Increased PAI-1 expression, which has been associated with obstructive VG disease, did not increase intimal hyperplasia.Decreased PAI-1 expression (1) promotes intimal hyperplasia by pathways that do not require vitronectin and (2) increases thrombin activity in VG. PAI-1 overexpression, although it promotes SMC migration in vitro, did not increase intimal hyperplasia. These results challenge the concept that PAI-1 drives nonthrombotic obstructive disease in VG and suggest that PAI-1's antiproteolytic function, including its antithrombin activity, inhibits intimal hyperplasia.
| S-EPMC3141099 | biostudies-literature
Project description:Various immune cells are involved in host tumor immune responses. In particular, there are many T cell subsets with different roles in tumor immunity. T-helper (Th) 1 cells are involved in cellular immunity and thus play the major role in host anti-tumor immunity by inducing and activating cytotoxic T lymphocytes (CTLs). On the other hand, Th2 cells are involved in humoral immunity and suppressive to Th1 responses. Regulatory T (Treg) cells negatively regulate immune responses and contribute to immune evasion of tumor cells. Th17 cells are involved in inflammatory responses and may play a role in tumor progression. However, recent studies have also shown that Th17 cells are capable of directly inducting CTLs and thus may promote anti-tumor immunity. Besides these T cell subsets, there are many other innate immune cells such as dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs) that are involved in host immune responses to cancer. The migratory properties of various immune cells are critical for their functions and largely regulated by the chemokine superfamily. Thus, chemokines and chemokine receptors play vital roles in the orchestration of host immune responses to cancer. In this review, we overview the various immune cells involved in host responses to cancer and their migratory properties regulated by the chemokine superfamily. Understanding the roles of chemokines and chemokine receptors in host immune responses to cancer may provide new therapeutic opportunities for cancer immunotherapy.
| S-EPMC8656932 | biostudies-literature
Project description:Living cells have developed a relay system to efficiently transfer sulfur (S) from cysteine to various thio-cofactors (iron-sulfur (Fe-S) clusters, thiamine, molybdopterin, lipoic acid, and biotin) and thiolated tRNA. The presence of such a transit route involves multiple protein components that allow the flux of S to be precisely regulated as a function of environmental cues to avoid the unnecessary accumulation of toxic concentrations of soluble sulfide (S2-). The first enzyme in this relay system is cysteine desulfurase (CSD). CSD catalyzes the release of sulfane S from L-cysteine by converting it to L-alanine by forming an enzyme-linked persulfide intermediate on its conserved cysteine residue. The persulfide S is then transferred to diverse acceptor proteins for its incorporation into the thio-cofactors. The thio-cofactor binding-proteins participate in essential and diverse cellular processes, including DNA repair, respiration, intermediary metabolism, gene regulation, and redox sensing. Additionally, CSD modulates pathogenesis, antibiotic susceptibility, metabolism, and survival of several pathogenic microbes within their hosts. In this review, we aim to comprehensively illustrate the impact of CSD on bacterial core metabolic processes and its requirement to combat redox stresses and antibiotics. Targeting CSD in human pathogens can be a potential therapy for better treatment outcomes.
| S-EPMC8300815 | biostudies-literature
Project description:Amicoumacin A (Ami) halts bacterial growth by inhibiting the ribosome during translation. The Ami binding site locates in the vicinity of the E-site codon of mRNA. However, Ami does not clash with mRNA, rather stabilizes it, which is relatively unusual and implies a unique way of translation inhibition. In this work, we performed a kinetic and thermodynamic investigation of Ami influence on the main steps of polypeptide synthesis. We show that Ami reduces the rate of the functional canonical 70S initiation complex (IC) formation by 30-fold. Additionally, our results indicate that Ami promotes the formation of erroneous 30S ICs; however, IF3 prevents them from progressing towards translation initiation. During early elongation steps, Ami does not compromise EF-Tu-dependent A-site binding or peptide bond formation. On the other hand, Ami reduces the rate of peptidyl-tRNA movement from the A to the P site and significantly decreases the amount of the ribosomes capable of polypeptide synthesis. Our data indicate that Ami progressively decreases the activity of translating ribosomes that may appear to be the main inhibitory mechanism of Ami. Indeed, the use of EF-G mutants that confer resistance to Ami (G542V, G581A, or ins544V) leads to a complete restoration of the ribosome functionality. It is possible that the changes in translocation induced by EF-G mutants compensate for the activity loss caused by Ami.
| S-EPMC7907450 | biostudies-literature
Project description:Despite active research in virotherapy, this apparently safe modality has not achieved widespread success. The immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. The challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. NK cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. Various reports have suggested that the NK response to oncolytic viral therapy is a critical factor in premature viral clearance while also mediating downstream antitumor immunity. As a result, particular attention should be given to the NK cell response to various oncolytic viral vectors and how their antiviral properties can be suppressed while maintaining tumor clearance. In this review we discuss the current literature on the NK response to oncolytic viral infection and how future studies clarify this intricate response.
| S-EPMC3263705 | biostudies-literature
Project description:Induced expression of neuroprotective genes is essential for maintaining neuronal integrity after stressful insults to the brain. Here we show that NR4A nuclear orphan receptors are induced after excitotoxic and oxidative stress in neurons, up-regulate neuroprotective genes, and increase neuronal survival. Moreover, we show that NR4A proteins are induced by cAMP response element binding protein (CREB) in neurons exposed to stressful insults and that they function as mediators of CREB-induced neuronal survival. Animals with null mutations in three of six NR4A alleles show increased oxidative damage, blunted induction of neuroprotective genes, and increased vulnerability in the hippocampus after treatment with kainic acid. We also demonstrate that NR4A and the transcriptional coactivator PGC-1alpha independently regulate distinct CREB-dependent neuroprotective gene programs. These data identify NR4A nuclear orphan receptors as essential mediators of neuroprotection after exposure to neuropathological stress.
| S-EPMC2901488 | biostudies-literature
Project description:More than half of the protein-coding genes in bacteria are organized in polycistronic operons composed of two or more genes. It remains under debate whether the operon organization maintains the stoichiometric expression of the genes within an operon. In this study, we performed a label-free data-independent acquisition hyper reaction monitoring mass-spectrometry (HRM-MS) experiment to quantify the Escherichia coli proteome in exponential phase and quantified 93.6% of the cytosolic proteins, covering 67.9% and 56.0% of the translating polycistronic operons in BW25113 and MG1655 strains, respectively. We found that the translational regulation contributes largely to the proteome complexity: the shorter operons tend to be more tightly controlled for stoichiometry than longer operons; the operons which mainly code for complexes is more tightly controlled for stoichiometry than the operons which mainly code for metabolic pathways. The gene interval (distance between adjacent genes in one operon) may serve as a regulatory factor for stoichiometry. The catalytic efficiency might be a driving force for differential expression of enzymes encoded in one operon. These results illustrated the multifaceted nature of the operon regulation: the operon unified transcriptional level and gene-specific translational level. This multi-level regulation benefits the host by optimizing the efficiency of the productivity of metabolic pathways and maintenance of different types of protein complexes.
| S-EPMC6544118 | biostudies-literature
Project description:Neuroinflammation is a key element of AD pathology and conceivably a result of a disturbed resolution. Resolution of inflammation is an active process which is strictly orchestrated following the acute inflammatory response after removal of the inflammatory stimuli. Acute inflammation is actively terminated by specialized pro-resolving mediators (SPMs) thereby promoting healing and return to homeostasis. Failed resolution may contribute to persistent neuroinflammation and aggravate AD pathology. BLT1 (leukotriene B4 receptor) and ChemR23 (chemerin receptor 23) are receptors for the SPM resolvin (Rv) E1 and are important clinical targets for ending inflammation. In AD, the levels of SPMs are decreased, and pro-inflammatory mediators are increased. In the current study, the distribution of BLT1 and ChemR23 receptors in control brains and in AD as well as correlations with AD pathology was examined for the first time. BLT1 and ChemR23 were analyzed in different regions of post-mortem human brain from cases with AD, early-onset AD and mild cognitive impairment (MCI) and healthy controls, using western blotting and immunohistochemistry. BLT1 and ChemR23 were detected in neurons and glial cells in all examined regions of the human brain, with markedly higher levels in AD than in controls. The receptor levels correlated with the density of staining for the inflammation markers HLA-DR and YKL-40 for microglia and astrocytes, respectively, and elevated staining coincided with high Braak stages in AD. The relative staining densities of these receptors were higher in the basal forebrain, cingulate gyrus and hippocampal regions compared to the cerebellum and frontal cortex (BA46). In conclusion, alterations in the expression of the resolution receptor BLT1 in AD have not been reported previously and the changes in both BLT1 and ChemR23 suggest a disturbed resolution pathway in several regions of the AD brain that may play a role in disease pathology.
| S-EPMC8018009 | biostudies-literature