ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage
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31.10.2019 |
Kostyusheva A.
Brezgin S.
Bayurova E.
Gordeychuk I.
Isaguliants M.
Goptar I.
Urusov F.
Nikiforova A.
Volchkova E.
Kostyushev D.
Chulanov V.
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Viruses |
10.3390/v11110997 |
1 |
Ссылка
Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.
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Effect of Medium pH And Ion Strength on the Thermal Stability of Plant Formate Dehydrogenases
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01.07.2018 |
Pometun A.
Voinova N.
Pometun E.
Savin S.
Tishkov V.
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Moscow University Chemistry Bulletin |
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0 |
Ссылка
© 2018, Allerton Press, Inc. The effect of medium pH and ion strength on the thermal stability of formate dehydrogenases (EC 1.2.1.2, FDH) from model plant Arabidopsis thaliana (AthFDH) and soybean Glycine max (SoyFDH) are studied. The dependence of the residual activity on time is described by the kinetics of the reaction of the first order in all the experimental conditions. The dependence of the first order thermal inactivation constants on phosphate buffer concentration has the form of a bell-shaped curve. It was found that an increase in the pH value resulted in an increase and decrase of inactivation rate constans for SoyFDH and AthFDH, respectively. The activation parameters of the thermal inactivation process, ΔH≠ and ΔS≠ are calculated from the experimental data at different medium pH values and phosphate buffer concentrations.
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New Missense Mutation His2026Arg in the Factor VIII Gene Was Revealed in Two Female Patients with Clinical Manifestation of Hemophilia A
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01.06.2018 |
Surin V.
Salomashkina V.
Pshenichnikova O.
Perina F.
Bobrova O.
Ershov V.
Budanova D.
Gadaev I.
Konyashina N.
Zozulya N.
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Russian Journal of Genetics |
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0 |
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© 2018, Pleiades Publishing, Inc. Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.
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Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor
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03.04.2018 |
Budnik I.
Shenkman B.
Hauschner H.
Zilinsky I.
Savion N.
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Platelets |
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2 |
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© 2018 Taylor & Francis. Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3–fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors. Platelet activation in platelet-rich plasma was evaluated by P-selectin expression using flow cytometry. Contribution of platelets to whole blood clotting was assessed by rotation thromboelastometry (ROTEM). Selective signaling of Gαq or Gαi but not Gα12/13 promoted P-selectin expression. Further enhancement of P-selectin expression was achieved by ADP-induced combined signaling of Gαq and Gαi, and to more extent by U46619 at high concentration (1.5 μM) induced combined signaling of Gαq and Gα12/13 while maximal P-selectin expression was achieved by thrombin receptor-activating peptide (TRAP)-induced combined signaling of Gαq, Gαi, and Gα12/13. In ROTEM, selective activation of Gαq, Gαi, or Gα12/13 failed to affect blood clotting. Combined signaling of Gαq and Gαi or Gαq and Gα12/13 or all three G proteins shortened the clotting time and stimulated clot strength. Pretreatment of platelets with acetylsalicylic acid did not change the effect of ADP but inhibited the effect of TRAP. Signaling of Gαq and Gα12/13 triggered by U46619 also stimulated clot formation. Combined signaling of either Gαq and Gαi or Gαq and Gα12/13 is sufficient to stimulate maximal platelet activation and enhanced clot formation in platelets treated with inhibitor of integrin αIIbβ3. It could be suggested that outside-in signaling is not necessarily required to fulfill these platelet functions.
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Sympathetic nervous system activation in pathogenesis of development of essential hypertension and its role in target-organs damage in young and middle aged adults: The cardioprotective capabilities of bisoprolol
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01.01.2018 |
Ostroumova O.
Kochetkov A.
Guseva T.
Zykova A.
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Kardiologiya |
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1 |
Ссылка
© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. The article discusses various mechanisms of developmentt and progression of arterial hypertension in young and middle aged adults. It emphasizes the predominant role of hypersympathicotonia in the development of the disease in this category of patients. Various mechanisms are considered, by means of which the increase of activity of the sympathetic nervous system leads to elevation of arterial pressure and potentiates early damage of target organs, first of all, damage of the heart. The data of numerous studies demonstrating pronounced cardioprotective effects of a highly selective representative of the class of β-blockers bisoprolol in young and middle aged hypertensive patients are presented.
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Worksite hypertension as a model of stress-induced arterial hypertension
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01.01.2018 |
Ostroumova O.
Kochetkov A.
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Terapevticheskii Arkhiv |
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1 |
Ссылка
© 2018 Media Sphera Publishing Group.All Rights Reserved. The review presents a modern view on stress as a risk factor for the development of arterial hypertension (AH). A variety pathogenic mechanisms responsible for increase of blood pressure during stress exposure are described in detail. The importance of the sympathetic activation as a key link in the development of stress-induced AH and initiation of a cascade of pathophysiological reactions that realize their adverse effects at the level of the whole organism is underlined. Particular attention is paid to worksite AH as a variant of stress-induced hypertension due to its wide prevalence and association with an increased risk of cardiovascular complications, primarily myocardial infarction and stroke. Epidemiological data and results of recent metanalysis are presented, indicating the high significance of job strain as a risk factor for adverse cardiovascular events. The actual psychological stress reduction programs are described. Possibilities of using β-blockers in patients with stress-induced hypertension as drugs affecting the central pathogenetic trigger of this disease are considered. The advantages of using bisoprolol as a highly selective β-blocker are considered taking into account the available body of evidence for its effectiveness in patients with worksite AH, as well as its metabolic neutrality and target-organ protective properties.
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Corrigendum: Early Growth Response Gene-2 Is Essential for M1 and M2 Macrophage Activation and Plasticity by Modulation of the Transcription Factor CEBPβ
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01.01.2018 |
Veremeyko T.
Yung A.
Anthony D.
Strekalova T.
Ponomarev E.
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Frontiers in immunology |
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0 |
Ссылка
[This corrects the article DOI: 10.3389/fimmu.2018.02515.].
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