Search results for "MTO"
showing 10 items of 538 documents
In human endothelial cells rapamycin causes mTORC2 inhibition and impairs cell viability and function.
2008
Aim Drug-eluting stents are widely used to prevent restenosis but are associated with late endothelial damage. To understand the basis for this effect, we have studied the consequences of a prolonged incubation with rapamycin on the viability and functions of endothelial cells. Methods and results Human umbilical vein or aorta endothelial cells were exposed to rapamycin in the absence or in the presence of tumour necrosis factor α (TNFα). After a 24 h-incubation, rapamycin (100 nM) caused a significant cell loss associated with the increase of both apoptosis and necrosis, as quantified by propidium iodide staining, caspase 3 activity, and lactate dehydrogenase release. Rapamycin also impair…
Coordinated Sumoylation and Ubiquitination Modulate EGF Induced EGR1 Expression and Stability
2011
Background Human early growth response-1 (EGR1) is a member of the zing-finger family of transcription factors induced by a range of molecular and environmental stimuli including epidermal growth factor (EGF). In a recently published paper we demonstrated that integrin/EGFR cross-talk was required for Egr1 expression through activation of the Erk1/2 and PI3K/Akt/Forkhead pathways. EGR1 activity and stability can be influenced by many different post-translational modifications such as acetylation, phosphorylation, ubiquitination and the recently discovered sumoylation. The aim of this work was to assess the influence of sumoylation on EGF induced Egr1 expression and/or stability. Methods We …
mTOR Driven Gene Transcription Is Required for Cholesterol Production in Neurons of the Developing Cerebral Cortex
2021
AbstractDysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the stero…
A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability
2017
AbstractProteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed…
Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells
2011
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…
UV photoexcitation of a dissolved metalloid Ge9 cluster compound and its extensive ultrafast response.
2015
Femtosecond pump-probe absorption spectroscopy in tetrahydrofuran solution has been used to investigate the dynamics of a metalloid cluster compound {Ge9[Si(SiMe3)3]3}(-). Upon UV photoexcitation, the transients in the near-infrared spectral region showed signatures reminiscent of excess electrons in THF (bound or quasi-free) whereas in the visible part excited state dynamics of the cluster complex dominates.
Acs mugurējās daļas izmaiņas pēc ķirurģiskās kataraktas operācijas ar femtolāzeru, salīdzinot ar ultraskaņas fakoemulsifikāciju
2016
Diplomdarbs ir uzrakstīts latviešu valodā uz 32 lapām, satur 18 attēlus, 1 tabulu, 2 pielikumus un 27 atsauces uz literatūras avotiem. Pētījuma mērķis: Novērot un salīdzināt kādas ir acs ābola mugurējās daļas izmaiņas pēc kataraktas operācijas ar femtolāzeru un ultraskaņu, kā arī salīdzināt abus operācijas veidus, lai turpmāk sniegtu pacientiem informāciju par riskiem un ieguvumiem. Metode: Tika pētīti 40 pacienti, no kuriem 20 tika veikta ultraskaņas fakoemulsifikācija un 20, kuriem tika veikta femtosekunžu lāzera (FSL) operācija. Jaunākais pētījuma grupas pacients bija 43 gadus vecs un vecākais 88 gadus vecs. Vidējais vecums 66,57 gadi. Rezultāti: Pēc US fakoemulsifikācijas komplikāciju s…
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart
2014
Abstract Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain‐ and loss‐of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor‐B (VEGF‐B) in the heart. A cardiomyocyte‐specific VEGF‐B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon ischemia‐reperfusion. VEGF‐B increased VEGF signals via VEGF receptor‐2 to activate Erk1/2, which resulted in vascular growth. Akt and mTORC1 pathways were upregulated and AMPK downregulated, …
Femtometer accuracy EXAFS measurements: Isotopic effect in the first, second and third coordination shells of germanium
2009
The analysis of the EXAFS signals from 70Ge and 76Ge has evidenced the low-temperature effect of isotopic mass difference on the amplitude of relative atomic vibrations. This effect is reflected in the difference of the Debye-Waller factors of the first three coordination shells, and on the difference of nearest-neighbour average interatomic distances, evaluated with femtometer accuracy. The experimental results are in agreement with theoretical expectations.
Anti-inflammatory Function of High-Density Lipoproteins via Autophagy of IκB Kinase
2015
Background & Aims: Plasma levels of high-density lipoprotein (HDL) cholesterol are frequently found decreased in patients with inflammatory bowel disease (IBD). Therefore, and because HDL exerts anti-inflammatory activities, we investigated whether HDL and its major protein component apolipoprotein A-I (apoA-I) modulate mucosal inflammatory responses in vitro and in vivo. Methods: The human intestinal epithelial cell line T84 was used as the in vitro model for measuring the effects of HDL on the expression and secretion of tumor necrosis factor (TNF), interleukin-8 (IL-8), and intracellular adhesion molecule (ICAM). Nuclear factor-κB (NF-κB)-responsive promoter activity was studied by …