Search results for " KINASE"
showing 10 items of 2352 documents
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC.
1994
We have analysed 118 families with inherited medullary thyroid carcinoma (MTC) for mutations of the RET proto-oncogene. These included cases of multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial MTC (FMTC). Mutations at one of 5 cysteines in the extracellular domain were found in 97% of patients with MEN 2A and 86% with FMTC but not in MEN 2B patients or normal controls. 84% of the MEN2A mutations affected codon 634. MEN 2A patients with a Cys634 to Arg substitution had a greater risk of developing parathyroid disease than those with other codon 634 mutations. Our data show a strong correlation between disease phenotype and the nature and position of the RET mutatio…
Regulated Proteolysis of RAGE and AβPP as Possible Link Between Type 2 Diabetes Mellitus and Alzheimer's Disease
2009
Epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of developing Alzheimer's disease (AD). In T2DM, the elevated blood glucose level promotes formation of advanced glycation end products (AGEs). The receptor for AGEs (RAGE) is a type I membrane-protein and is also able to import amyloid-beta (Abeta) from the blood across the blood-brain-barrier into the brain. Oligomeric Abeta peptides disturb synaptic function in the brain and are believed to contribute to the development of AD. Abeta peptides are released from the amyloid-beta protein precursor (AbetaPP) after sequential proteolysis by beta- and gamma-secretases but alpha-secretase-mediated cleavage…
Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone
2009
CRH is a major central stress mediator, but also a potent neuroprotective effector. The mechanisms by which CRH mediates its neuroprotective actions are largely unknown. Here, we describe that the gap junction molecule connexin43 (Cx43) mediates neuroprotective effects of CRH toward experimentally induced oxidative stress. An enhanced gap junction communication has been reported to contribute to neuroprotection after neurotoxic insults. We show that CRH treatment up-regulates Cx43 expression and gap junctional communication in a CRH receptor-dependent manner in IMR32 neuroblastoma cells, primary astrocytes, and organotypic hippocampal slice cultures. MAPKs and protein kinase A-cAMP response…
Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling
2015
Cardiac hypertrophy accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease, and it is a strong predictor of increased cardiovascular morbidity and mortality. Deletion of bone marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has been shown to inhibit cardiac hypertrophy in mice. This finding raised the possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced cardiac hypertrophy is significantly reduced in mice deficient i…
The Effects of Alcohol Consumption on Recovery Following Resistance Exercise: A Systematic Review
2019
Background: The aim of this manuscript was to describe the effects of alcohol ingestion on recovery following resistance exercise. Methods: A literature search was performed using the following database: Web of Science, NLM Pubmed, and Scopus. Studies regarding alcohol consumption after resistance exercise evaluating recovery were considered for investigation. The main outcomes took into account biological, physical and cognitive measures. Multiple trained researchers independently screened eligible studies according to the eligibility criteria, extracted data and assessed risk of bias. Results: A total of 12 studies were considered eligible and included in the quantitative synthesis: 10 in…
Bafetinib inhibits functional responses of human eosinophils in vitro
2012
Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively).…
Protein kinase C-inhibiting properties of the losartan metabolite EXP3179 make the difference.
2009
The inhibition of the renin-angiotensin axis with the angiotensin II (ATII) receptor blockers, such as losartan, candesartan, and valsartan, has been demonstrated, similar to angiotensin-converting enzyme inhibitors, to reduce mortality in patients with arterial hypertension, chronic congestive heart failure, and acute myocardial infarction.1 Initially, the ATII receptor antagonist losartan helped to demonstrate new classes of ATII receptors and substantially expanded our knowledge about the cardiovascular effects of the renin-angiotensin-aldosterone system and its effector peptide ATII. Researchers dealing with this compound soon revealed that, beyond its antihypertensive effects attribute…
FLT3 as a therapeutic target in AML: still challenging after all these years
2010
Abstract Mutations within the FMS-like tyrosine kinase 3 (FLT3) gene on chromosome 13q12 have been detected in up to 35% of acute myeloid leukemia (AML) patients and represent one of the most frequently identified genetic alterations in AML. Over the last years, FLT3 has emerged as a promising molecular target in therapy of AML. Here, we review results of clinical trials and of correlative laboratory studies using small molecule FLT3 tyrosine kinase inhibitors (TKIs) in AML patients. We also review mechanisms of primary and secondary drug resistance to FLT3-TKI, and from the data currently available we summarize lessons learned from FLT3-TKI monotherapy. Finally, for using FLT3 as a molecul…
Recovery of Inflammation, Cardiac, and Muscle Damage Biomarkers After Running a Marathon
2019
Bernat-Adell, MD, Collado-Boira, EJ, Moles-Julio, P, Panizo-González, N, Martínez-Navarro, I, Hernando-Fuster, B, and Hernando-Domingo, C. Recovery of inflammation, cardiac and muscle damage biomarkers after running a marathon. J Strength Cond Res 35(3): 626-632, 2021-Physical endurance sports conditions the increase of blood biomarkers responsible for the acute inflammatory response. The purpose of this study was to observe the impact of intense physical exercise on these biomarkers and detect their recovery pattern. This is an experimental study of repeated measures (pre-post marathon). The biomarkers lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity troponin T (hs-TNT),…
Muscle cramping in the marathon: dehydration and electrolyte depletion vs. muscle damage
2020
Martinez-Navarro, I, Montoya-Vieco, A, Collado, E, Hernando, B, Panizo, N, and Hernando, C. Muscle Cramping in the marathon: Dehydration and electrolyte depletion vs. muscle damage. J Strength Cond Res XX(X): 000-000, 2020-Our aim was to compare dehydration variables, serum electrolytes, and muscle damage serum markers between runners who suffered exercise-associated muscle cramps (EAMC) and runners who did not suffer EAMC in a road marathon. We were also interested in analyzing race pacing and training background. Nighty-eight marathoners took part in the study. Subjects were subjected to a cardiopulmonary exercise test. Before and after the race, blood and urine samples were collected and…