Search results for "DNA"
showing 10 items of 6803 documents
Rac1-Regulated Endothelial Radiation Response Stimulates Extravasation and Metastasis That Can Be Blocked by HMG-CoA Reductase Inhibitors
2011
Radiotherapy (RT) plays a key role in cancer treatment. Although the benefit of ionizing radiation (IR) is well established, some findings raise the possibility that irradiation of the primary tumor not only triggers a killing response but also increases the metastatic potential of surviving tumor cells. Here we addressed the question of whether irradiation of normal cells outside of the primary tumor augments metastasis by stimulating the extravasation of circulating tumor cells. We show that IR exposure of human endothelial cells (EC), tumor cells (TC) or both increases TC-EC adhesion in vitro. IR-stimulated TC-EC adhesion was blocked by the HMG-CoA reductase inhibitor lovastatin. Glycyrr…
Rac1 and PAK1 are upstream of IKK-ε and TBK-1 in the viral activation of interferon regulatory factor-3
2004
The anti-viral type I interferon (IFN) response is initiated by the immediate induction of IFN beta, which is mainly controlled by the IFN-regulatory factor-3 (IRF-3). The signaling pathways mediating viral IRF-3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF-3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFN beta promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF-3, we have identified the kinase p21-activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF-3 activators, I kappa B kinase- and TANK-binding kina…
Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters
2002
In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for 32P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall 32P-GTP binding acvitity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhance…
Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.
2012
To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia m…
Jokirapujen ja täplärapujen esiintymisen selvittäminen eDNA-menetelmällä
2021
Vaarantuneiden jokirapukantojen uhkana on vesistöihimme hyvin sopeutunut vieraslaji, täplärapu, ja sen kantama, erityisesti jokiravuille kohtalokas rapuruton muoto. Rapupopulaatioiden paikantaminen ja seuranta on perinteisesti perustunut paikallistietoon ja koeravustuksiin. Viime vuosien aikana ympäristö-DNA:n (eDNA) käyttöön perustuvat menetelmät ovat kehittyneet varteenotettavaksi vaihtoehdoksi perinteisten menetelmien rinnalle. eDNA-menetelmän avulla voidaan vesinäytteestä tunnistaa kohde-eliöt molekyylibiologisin menetelmin. Tämän tutkimuksen tarkoituksena oli selvittää, soveltuuko eDNA-menetelmä käytettäväksi rapupopulaatioiden havainnoinnissa suomalaisissa vesistöissä ja verrata saatu…
The state and prospects of development of alternative energy sources in Ukraine
2017
Przedstawiono wyniki analizy systemu państwowej regulacji oraz wspierania procesów wykorzystania OZE na Ukrainie. Podkreślono główne mechanizmy promocji energii ze źródeł odnawialnych oraz alternatywnych. Oszacowano potencjał energii słonecznej, wiatrowej i wodnej, biomasy jako źródła paliw twardych, płynnych i gazowych.
The genome sequence of Blochmannia floridanus: Comparative analysis of reduced genomes
2003
Bacterial symbioses are widespread among insects, probably being one of the key factors of their evolutionary success. We present the complete genome sequence of Blochmannia floridanus , the primary endosymbiont of carpenter ants. Although these ants feed on a complex diet, this symbiosis very likely has a nutritional basis: Blochmannia is able to supply nitrogen and sulfur compounds to the host while it takes advantage of the host metabolic machinery. Remarkably, these bacteria lack all known genes involved in replication initiation ( dna A, pri A, and rec A). The phylogenetic analysis of a set of conserved protein-coding genes shows that Bl. floridanus is phylogenetically related to Buch…
Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis
2019
Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. Methods: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinic…
Rho GTPases Are Involved in the Regulation of NF-κB by Genotoxic Stress
2001
A common cellular response to genotoxic agents and inflammatory cytokines is the activation of NF-kappaB. Here, we addressed the question of whether small GTPases of the Rho family are involved in the stimulation of NF-kappaB signaling by genotoxic agents or TNFalpha in HeLa cells. Inhibition of isoprenylation of Rho proteins by use of the HMG-CoA reductase inhibitor lovastatin attenuated UV-, doxorubicin-, and TNFalpha-induced degradation of IkappaBalpha as well as drug-stimulated DNA binding activity of NF-kappaB. Furthermore, NF-kappaB-regulated gene expression stimulated by either UV irradiation or treatment with TNFalpha was abrogated by lovastatin pretreatment. This indicates that iso…
Late Activation of Stress-activated Protein Kinases/c-Jun N-terminal Kinases Triggered by Cisplatin-induced DNA Damage in Repair-defective Cells
2011
Although stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) are rapidly activated by genotoxins, the role of DNA damage in this response is not well defined. Here we show that the SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK (Thr-183/Tyr-185) correlates with the level of cisplatin-DNA adducts at late times (16–24 h) after drug treatment in both human and mouse cells. Transfection of platinated plasmid DNA also caused SAPK/JNK activation. A defect in transcription-coupled nucleotide excision repair resting on a mutation in Cockayne syndrome group B protein promoted the late SAPK/JNK activation following cisplatin exposure. Signaling to SAPK/JNK was accompanied by act…