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DNA Repair Feb 2016The focus of this article is on the DNA binding and ATPase activities of the mismatch repair (MMR) protein, MutS-our current understanding of how this protein uses ATP... (Review)
Review
The focus of this article is on the DNA binding and ATPase activities of the mismatch repair (MMR) protein, MutS-our current understanding of how this protein uses ATP to fuel its actions on DNA and initiate repair via interactions with MutL, the next protein in the pathway. Structure-function and kinetic studies have yielded detailed views of the MutS mechanism of action in MMR. How MutS and MutL work together after mismatch recognition to enable strand-specific nicking, which leads to strand excision and synthesis, is less clear and remains an active area of investigation.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Base Pair Mismatch; DNA Mismatch Repair; Humans; MutS DNA Mismatch-Binding Protein; Signal Transduction
PubMed: 26704427
DOI: 10.1016/j.dnarep.2015.11.017 -
IEEE/ACM Transactions on Computational... 2019Myosin V is a processive doubled-headed biomolecular motor involved in many intracellular organelle and vesicle transport. The unidirectional movement is coupled with...
Myosin V is a processive doubled-headed biomolecular motor involved in many intracellular organelle and vesicle transport. The unidirectional movement is coupled with the adenosine triphosphate (ATP) hydrolysis and product release cycle. With the progress of experimental techniques and the enhancement of measuring directness, detailed knowledge of the motility of myosin V has been obtained. Following the ATPase cycle, the 4-state mechanochemical model of the myosin V's processive movement is used. The transitions between various states take place in a stochastic manner. We can use the master equation to analyze and calculate quantitatively. Meanwhile, the effect of the reverse reaction is taken fully into account. We fit the mean velocity, the mean dwell time, the mean run length, and the ratio of forward/backward steps as a functionof ATP, ADP, and Pi concertration. The theoretical curves are generally in line with the experimental data. This work provides a new insight for the characteristic of myosin V.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Algorithms; Computational Biology; Humans; Hydrolysis; Kinetics; Models, Molecular; Myosin Type V; Pressure; Reproducibility of Results; Stochastic Processes; Stress, Mechanical
PubMed: 28212094
DOI: 10.1109/TCBB.2017.2669311 -
BMC Cardiovascular Disorders Jan 2023The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou...
BACKGROUND
The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou population and to determine associations between P2Y1 and P2Y12 genotypes and ADP-induced platelet aggregation in this population.
METHODS
All subjects were screened for P2Y1 (c.1622A > G) and P2Y12 (H1/H2, c.34C > T) polymorphisms by direct DNA sequencing. The maximal platelet aggregation rate (MAR) in AMI patients (n = 61) and healthy control subjects (n = 50) was measured by a PL-12 platelet function analyzer, and adenosine diphosphate (ADP) (5 μmol/L) was used as an agonist.
RESULTS
The haploid H2 allele in the P2Y12 gene was more frequent in patients with AMI than in control subjects (OR 1.887, P = 0.005). The P2Y12 H2 haplotype was significantly associated with AMI in the codominant (P = 0.008), dominant (OR 2.103, P = 0.003), and overdominant models (OR 2.133, P = 0.003). After adjusting for potential confounders, H2 haplotype carriers had a 2.132-fold increased risk for AMI (OR 2.132, P = 0.012) compared with noncarriers. Moreover, we observed that the ADP-induced MAR in the carriers of the H2 haplotype from the control group was somewhat higher than that in noncarriers of this group (P = 0.020). However, we failed to demonstrate that the P2Y1 H1/H2 polymorphism affected ADP-induced MAR in AMI patients. Additionally, P2Y1 c.1622A > and P2Y12 c.34C > T polymorphisms were not associated with the risk of AMI or ADP-induced MAR in either group.
CONCLUSIONS
Therefore, our results suggest that the P2Y12 H2 haplotype was associated with a higher risk of AMI, while its effect on increased ADP-induced platelet aggregation remains to be investigated. Thus, the P2Y12 H2 haplotype may be a potential marker for AMI.
Topics: Humans; Platelet Aggregation; Adenosine Diphosphate; Polymorphism, Genetic; Platelet Aggregation Inhibitors; Myocardial Infarction; Blood Platelets
PubMed: 36681816
DOI: 10.1186/s12872-023-03075-4 -
Current Topics in Microbiology and... 2017Binary actin-ADP-ribosylating toxins (e.g., Clostridium botulinum C2 toxin or Clostridium perfringens iota toxin ) consist of two separate proteins: An... (Review)
Review
Binary actin-ADP-ribosylating toxins (e.g., Clostridium botulinum C2 toxin or Clostridium perfringens iota toxin ) consist of two separate proteins: An ADP-ribosyltransferase, which modifies actin thereby inhibiting actin polymerization, and a binding component that forms heptamers after proteolytic activation. While C2 toxin interacts with carbohydrate structures on host cells, the group of iota-like toxins binds to lipolysis-stimulated lipoprotein receptor (LSR). Here, we review LSR and discuss the role and function of LSR in interaction of iota-like toxins with host cells.
Topics: ADP Ribose Transferases; Actins; Adenosine Diphosphate; Bacterial Toxins; Botulinum Toxins; Protein Binding; Protein Transport
PubMed: 27817176
DOI: 10.1007/82_2016_46 -
Annual Review of Biochemistry Jun 2021This volume of the contains three reviews on membrane channel proteins: the first by Szczot et al., titled The Form and Function of PIEZO2; the second by Ruprecht &...
This volume of the contains three reviews on membrane channel proteins: the first by Szczot et al., titled The Form and Function of PIEZO2; the second by Ruprecht & Kunji, titled Structural Mechanism of Transport of Mitochondrial Carriers; and the third by McIlwain et al., titled Membrane Exporters of Fluoride Ion. These reviews provide nice illustrations of just how far evolution has been able to play with the basic helix-bundle architecture of integral membrane proteins to produce membrane channels and transporters of widely different functions.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Fluorides; Ion Channels
PubMed: 34153216
DOI: 10.1146/annurev-biochem-010421-023239 -
Journal of Clinical Research in... Feb 2023Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet...
OBJECTIVE
Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients.
METHODS
The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method.
RESULTS
There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001).
CONCLUSION
Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.
Topics: Humans; Female; Platelet Aggregation; Adrenarche; Androgens; Puberty, Precocious; Adenosine Diphosphate; Collagen
PubMed: 36264033
DOI: 10.4274/jcrpe.galenos.2022.2022-6-13 -
Chemistry and Physics of Lipids Nov 2018Platelets are major targets for the treatment of thrombo-embolic disorders. Their plasma membrane contains specialized microdomains enriched in sphingomyelins and free...
Platelets are major targets for the treatment of thrombo-embolic disorders. Their plasma membrane contains specialized microdomains enriched in sphingomyelins and free cholesterol including membrane receptors. P2Y12 receptors need to be situated in these domains to be able to conduct activation signaling by adenosine diphosphate (ADP). We studied the impact of ticagrelor, a P2Y12 antagonist, and ADP on the composition and distribution of sphingomyelins in detergent-resistant membrane (DRM) of platelet membranes. Platelets were obtained from healthy donors. DRMs of platelet membranes were isolated in 4 experimental groups: control; ADP, with platelets stimulated by 20 μM ADP and 5 mM CaCl2; ticagrelor, with platelets incubated by ticagrelor 4 μM methanol dissolved; and ticagrelor + ADP, with incubation by ticagrelor followed by stimulation by ADP as above. After mass spectrometry analysis, we found 16 species of sphingomyelins in platelet membrane DRMs. We also found that treatment with ticagrelor and stimulation by ADP could induce changes in the composition, distribution and concentration of sphingomyelins in membranes of platelets. In all groups, the predominant species of sphingomyelins in platelet membrane was d18:1/16:0. Taken together, our results show that stimulation by ADP or inhibition by ticagrelor changed the level and composition of sphingomyelins in platelet membranes. These changes might be considered as reorganization or new recruitment of certain types of sphingomyelins through the membrane.
Topics: Adenosine Diphosphate; Cell Membrane; Sphingomyelins; Ticagrelor
PubMed: 30222974
DOI: 10.1016/j.chemphyslip.2018.09.008 -
Acta Pharmacologica Sinica Apr 2022Ion channels are ubiquitously expressed in almost all living cells, and are the third-largest category of drug targets, following enzymes and receptors. The transient... (Review)
Review
Ion channels are ubiquitously expressed in almost all living cells, and are the third-largest category of drug targets, following enzymes and receptors. The transient receptor potential melastatin (TRPM) subfamily of ion channels are important to cell function and survival. Studies have shown upregulation of the TRPM family of ion channels in various brain tumours. Gliomas are the most prevalent form of primary malignant brain tumours with no effective treatment; thus, drug development is eagerly needed. TRPM2 is an essential ion channel for cell function and has important roles in oxidative stress and inflammation. In response to oxidative stress, ADP-ribose (ADPR) is produced, and in turn activates TRPM2 by binding to the NUDT9-H domain on the C-terminal. TRPM2 has been implicated in various cancers and is significantly upregulated in brain tumours. This article reviews the current understanding of TRPM2 in the context of brain tumours and overviews the effects of potential drug therapies targeting TRPM2 including hydrogen peroxide (HO), curcumin, docetaxel and selenium, paclitaxel and resveratrol, and botulinum toxin. It is long withstanding knowledge that gliomas are difficult to treat effectively, therefore investigating TRPM2 as a potential therapeutic target for brain tumours may be of considerable interest in the fields of ion channels and pharmacology.
Topics: Adenosine Diphosphate Ribose; Brain Neoplasms; Calcium; Humans; Hydrogen Peroxide; Oxidative Stress; TRPM Cation Channels
PubMed: 34108651
DOI: 10.1038/s41401-021-00679-4 -
The Journal of Surgical Research Nov 2022Patients who undergo splenectomy (SPLN) have an estimated 10%-35% risk of venous thromboembolic events; however, the underlying mechanism and strategy for prevention...
INTRODUCTION
Patients who undergo splenectomy (SPLN) have an estimated 10%-35% risk of venous thromboembolic events; however, the underlying mechanism and strategy for prevention have yet to be identified. The goals of this study were to 1) investigate platelet aggregation after SPLN, 2) examine if aspirin administration could mitigate this effect, and 3) determine if concomitant hemorrhage would affect post-SPLN platelet function and response to aspirin.
METHODS
Murine models of operative SPLN and submandibular bleed (SMB) were utilized. Mice were randomized to eight groups as follows: untouched, SPLN, sham (laparotomy only), SMB, SPLN + SMB, SPLN + aspirin (ASA), SMB + ASA, and SPLN + SMB + ASA. Aspirin (50 mg/kg) was administered on postoperative days (PODs) one and two via oral gavage. Mice were euthanized on POD 3, platelet counts were obtained, and blood samples were analyzed via rotational thromboelastometry and impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists.
RESULTS
By POD 3, SPLN mice displayed a significant thrombocytosis compared to untouched, SMB, and sham SPLN mice. Clotting time and clot formation time were significantly decreased in SPLN and SPLN + SMB cohorts compared to untouched and sham controls with elevated mean clot firmness. SPLN mice also displayed a significant increase in ADP- and AA-mediated platelet aggregability compared to untouched controls, SMB, and SPLN + SMB. ASA significantly decreased platelet aggregation via both ADP and AA signaling in SPLN and SPLN + SMB cohorts without affecting viscoelastic coagulation testing.
CONCLUSIONS
Platelet hyperaggregability after SPLN is mediated by both ADP and AA signaling. Early aspirin administration may prevent increased platelet aggregation exacerbated after polytrauma.
Topics: Animals; Mice; Adenosine Diphosphate; Arachidonic Acid; Aspirin; Blood Platelets; Disease Models, Animal; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Splenectomy
PubMed: 35921721
DOI: 10.1016/j.jss.2022.06.026 -
Journal of Gynecology Obstetrics and... Apr 2022This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer.
METHODS
Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis.
RESULTS
A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06).
CONCLUSION
PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.
Topics: Adenosine Diphosphate; Adenosine Diphosphate Ribose; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Ribose
PubMed: 35218983
DOI: 10.1016/j.jogoh.2022.102344