Search results for "protein"
showing 10 items of 21431 documents
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…
Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis.
2005
Objective— Sedentary lifestyle is associated with increased cardiovascular events. The underlying molecular mechanisms are incompletely understood. Reactive oxygen species (ROS) contribute to endothelial dysfunction and atherosclerosis. An important source of vascular ROS is the NADPH oxidase. Methods and Results— C57BL6 mice were subjected to regular housing (physical inactivity) or voluntary training on running wheels (6 weeks). Inactivity increased vascular lipid peroxidation to 148±9% and upregulated superoxide release to 176±17% (L-012 chemiluminescence) and 188±29% (cytochrome C reduction assay), respectively. ROS production was predominantly increased in the endothelium and the medi…
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…
Molecular Mechanisms of the Blockage of Glioblastoma Motility
2021
Glioblastoma (GBM) is the most common and lethal brain tumor. GBM has a remarkable degree of motility and is able to infiltrate the healthy brain. In order to perform a rationale-based drug-repositioning study, we have used known inhibitors of two small Rho GTPases, Rac1 and Cdc42, which are upregulated in GBM and are involved in the signaling processes underlying the orchestration of the cytoskeleton and cellular motility. The selected inhibitors (R-ketorolac and ML141 for Cdc42 and R-ketorolac and EHT 1864 for Rac1) have been successfully employed to reduce the infiltration propensity of GBM in live cell imaging studies. Complementarily, all-atom simulations have elucidated the molecular …
Raman analysis of insulin denaturation induced by high-pressure and thermal treatments
2012
Raman spectroscopy has been used to investigate different conformational states of bovine pancreatic insulin: the native form and several structurally modified states with different extent of denaturation induced by thermo-chemical treatment and by applying very high pressure (up to 8 GPa) using a diamond anvil cell. High-pressure results confirm the peculiar strength to volume compression of insulin and largely extend the pressure range of its structural stability (0-4.2 GPa). Above 4.2 GPa, insulin undergoes an irreversible structural transition that, once pressure is released, leaves the sample in a new conformational state. The protein secondary structure after the pressure treatment re…
Proteins in Ionic Liquids: Reactions, Applications, and Futures
2019
Biopolymer processing and handling is greatly facilitated by the use of ionic liquids, given the increased solubility, and in some cases, structural stability imparted to these molecules. Focussing on proteins, we highlight here not just the key drivers behind protein-ionic liquid interactions that facilitate these functionalities, but address relevant current and potential applications of protein-ionic liquid interactions, including areas of future interest.
Antitumor Effect of Cabozantinib in Bone Metastatic Models of Renal Cell Carcinoma
2021
Background: The presence of bone metastases in renal cell carcinoma (RCC) negatively affects patients’ survival. Data from clinical trials has highlighted a significant benefit of cabozantinib in bone metastatic RCC patients. Here, we evaluated the antitumor effect of cabozantinib in coculture models of renal cell carcinoma (RCC) and osteoblasts (OBs) to investigate whether and how its antiproliferative activity is influenced by OBs. Methods: Bone/RCC models were generated, coculturing green fluorescent protein (GFP)-tagged Caki-1 and 786-O cells with human primary OBs in a “cell–cell contact” system. RCC proliferation and the OB molecular profile were evaluated after the cabozantinib treat…
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…