Search results for "SIGNALING"
showing 10 items of 1125 documents
PathVisio Analysis: An Application Targeting the miRNA Network Associated with the p53 Signaling Pathway in Osteosarcoma
2021
MicroRNAs (miRNAs) are small single-stranded, non-coding RNA molecules involved in the pathogenesis and progression of cancer, including osteosarcoma. We aimed to clarify the pathways involving miRNAs using new bioinformatics tools. We applied WikiPathways and PathVisio, two open-source platforms, to analyze miRNAs in osteosarcoma using miRTar and ONCO.IO as integration tools. We found 1298 records of osteosarcoma papers associated with the word "miRNA". In osteosarcoma patients with good response to chemotherapy, miR-92a, miR- 99b, miR-193a-5p, and miR-422a expression is increased, while miR-132 is decreased. All identified miRNAs seem to be centered on the TP53 network. This is the first …
The small heat-shock protein α B-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis
2014
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is stron…
Gene therapy with growth factors for periodontal tissue engineering : a review
2011
The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microen…
Role of calcium in E-selectin induced phenotype of T84 colon carcinoma cells
2003
The adhesion of cancer cells to the endothelium during the metastatic process involves the interaction of specific cell-cell adhesion receptors on the cell surface. E-selectin on endothelial cells and sialyl Lewis X carbohydrate component on tumor cells are mainly implicated in the adhesion of colon carcinoma cells to the endothelium of target organ. In this paper we show that binding of E-selectin to T84 colon tumor cells causes approximately a twofold increase in intracellular calcium concentration. In particular, using two inhibitors of receptor operated calcium channels, CAI and SK&F 96365, we present evidences that the augmentation in cytoplasmic calcium originates from ionic influx fr…
Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy
2013
Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 affected individuals. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homolog of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies showed a severe block in autophagosomal clearance in muscle a…
TORC1 controls G1–S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway
2015
The target of rapamycin complex 1 (TORC1) pathway couples nutrient, energy and hormonal signals with eukaryotic cell growth and division. In yeast, TORC1 coordinates growth with G1–S cell cycle progression, also coined as START, by favouring the expression of G1 cyclins that activate cyclin-dependent protein kinases (CDKs) and by destabilizing the CDK inhibitor Sic1. Following TORC1 downregulation by rapamycin treatment or nutrient limitation, clearance of G1 cyclins and C-terminal phosphorylation of Sic1 by unknown protein kinases are both required for Sic1 to escape ubiquitin-dependent proteolysis prompted by its flagging via the SCFCdc4 (Skp1/Cul1/F-box protein) ubiquitin ligase complex.…
Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes
2014
Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver gluc…
Potential and limitations of PKA/ PKG inhibitors for platelet studies
2021
Cyclic nucleotides (cAMP and cGMP) and corresponding protein kinases, protein kinase A (PKA) and protein kinase G (PKG), are the main intracellular mediators of endothelium-derived platelet inhibitors. Pharmacological PKA/PKG inhibitors are often used to discriminate between these two kinase activities and to analyze their underlying mechanisms. Previously we showed that all widely used PKG inhibitors (KT5823, DT3, RP isomers) either did not inhibit PKG or inhibited and even activated platelets independently from PKG. In this study, we examined several PKA inhibitors as well as inhibitors of adenylate and guanylate cyclases to reveal their effects on platelets and establish whether they are…
Clonidine increases membrane-associated phospholipase A2
2005
Background and objective: An anti-inflammatory effect of α 2 -adrenoreceptor agonists has been suggested. Phospholipase A 2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A 2 activity in an established in vitro model. Methods: Human being platelet membranes containing active phospholipase A 2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A 2 was measured by a radioisotope technique. Results: A massive increase in phospholipase A 2 activity was measured after clonidine exposure leading to final values of 92.5 ′ 3.1 pmol …
Phosphorylation of CalDAG-GEFI by protein kinase A prevents Rap1b activation.
2013
Summary Background Signaling via protein kinase A (PKA) and protein kinase G (PKG) is critical for maintaining platelets in the resting state. Both kinases down-regulate the activity of the small GTPase Rap1b, a critical signaling switch for integrin activation and platelet aggregation. However, the mechanism of Rap1b regulation by PKA and PKG is largely unknown. Objective To identify the PKA phosphorylation sites in calcium and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), the main GEF for Rap1b in platelets, and the effect of CalDAG-GEFI phosphorylation in Rap1b activation. Methods The phosphorylation sites in CalDAG-GEFI were identified by radio-active phos…