Search results for "Mitogen-Activated Protein Kinase"

Systematic review of BRAF/MEK inhibitors‐induced Severe Cutaneous Adverse Reactions (SCARs)

2020

Severe cutaneous adverse reactions (SCARs) [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF-mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi-induced SCARs. A systematic search of the following terms: 'vemurafenib', 'cobimetinib', 'dabrafenib', 'trametinib',…

Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways.

2010

Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect of aclidinium, a new long-acting muscarinic antagonist, on MUC5AC expression in human airway epithelial cells. MUC5AC mRNA (RT-PCR) and protein expression (ELISA and immunohistochemistry) were studied in human bronchial tissue and differentiated human airway epithelial cells activated with carbachol (100 μM) or cigarette smoke extract in the absence or presence of aclidinium. Carbachol increased MUC5AC mRNA and protein expression in human bronchus and cultured epithelial cells. Aclidinium inhibited the carbachol-induced MUC…

Regulation of endothelial nitric oxide synthase (eNOS) in myocardium subjected to cardioplegic arrest.

2009

BACKGROUND: Nitric oxide (NO) production by both coronary endothelial cells and cardiomyocytes is thought to play a significant role in myocardial pathophysiology following ischemia/reperfusion (I/R). METHODS: In thirteen pigs subjected to 1 hour cardioplegic arrest (CA) on CPB, left ventricular (LV) biopsies were collected prior to CPB (baseline), at 60 min CPA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. LV specimens were immunocytochemically stained against phospho-eNOS Ser1177 , phospho-eNOS Thr495 , phosphorylated ERK1/2, and AKT/PKB. Four additional pigs without CA served as controls. Cardiomyocytes were quantitatively investigated using TV densitometry (gray units: …

Clostridium difficile toxin A induces expression of the stress-induced early gene product RhoB.

2004

Clostridium difficile toxin A monoglucosylates the Rho family GTPases Rho, Rac, and Cdc42. Glucosylation leads to the functional inactivation of Rho GTPases and causes disruption of the actin cytoskeleton. A cDNA microarray revealed the immediate early gene rhoB as the gene that was predominantly up-regulated in colonic CaCo-2 cells after treatment with toxin A. This toxin A effect was also detectable in epithelial cells such as HT29 and Madin-Darby canine kidney cells, as well as NIH 3T3 fibroblasts. The expression of RhoB was time-dependent and correlated with the morphological changes of cells. The up-regulation of RhoB was approximately 15-fold and was based on the de novo synthesis of …

Age-dependent regulation of antioxidant genes by p38α MAPK in the liver

2018

p38α is a redox sensitive MAPK activated by pro-inflammatory cytokines and environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work was to assess whether p38α controls the antioxidant defense in the liver, and if so, to elucidate the mechanism(s) involved and the age-related changes. For this purpose, we used liver-specific p38α-deficient mice at two different ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young p38α knock-out mice exhibited a decrease in GSH levels and an increase in GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in p38α had higher hepatic GSH levels and lower GSSG/GSH ratio than young p38α knock-…

Activation of mitogen-activated protein kinase by the bradykinin B2receptor is independent of receptor phosphorylation and phosphorylation-triggered …

1999

Recent evidence suggests that serine/threonine phosphorylation and internalization of beta2-adrenergic receptors play critical roles in signalling to the mitogen-activated protein kinase cascade. To investigate whether this represents a general mechanism employed by G protein-coupled receptors, we studied the requirement of these processes in the activation of mitogen-activated protein kinase by G alpha(q)-coupled bradykinin B2 receptors. Mutant B2 receptors impaired in receptor phosphorylation and internalization are fully capable to activate mitogen-activated protein kinase. Bradykinin-induced long-term effects on mitogenic signalling monitored by measuring the transcriptional activity of…

Decreased SAPK/JNK signalling affects cytokine release and STAT3 activation in psoriatic fibroblasts.

2015

Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis.

2013

Abstract Ethnopharmacological relevance Pomegranate (Punica granatum L.; Lythraceae) has traditionally been used for the treatment of various inflammatory diseases, including ulcerative colitis (UC). Because its fruits and extracts are rich in ellagitannins, which release ellagic acid when hydrolyzed, consumption of pomegranate products is currently being widely promoted for their potential health effects, including the prevention of inflammatory diseases and cancer. To evaluate the anti-inflammatory effects of ellagic acid on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in two different strains of mice and to elucidate its possible mechanisms of action. Mater…

Yeast karyopherins Kap123 and Kap95 are related to the function of the cell integrity pathway

2009

The characterization of mutant strains in the gene encoding karyopherin Kap123 has revealed several morphogenetic defects. Inactivation of KAP123 caused alterations in the actin cytoskeleton, resulting in hyperpolarization and resistance to the actin polymerization inhibitor latrunculin B. In fact, the level of actin filaments is increased in kap123 mutant cells. In addition to the defect in actin cytoskeleton, the kap123 mutant cells showed a weakened cell wall, cell lysis and a growth defect in either the presence of sodium dodecyl sulfate or at high temperatures, which is alleviated by osmotic stabilizers. These defects in cell integrity and the actin cytoskeleton suggested a relationshi…

The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes

2003

Regulation of gene expression by mitogen-activated protein kinases (MAPKs) is essential for proper cell adaptation to extracellular stimuli. Exposure of yeast cells to high osmolarity results in rapid activation of the MAPK Hog1, which coordinates the transcriptional programme required for cell survival on osmostress. The mechanisms by which Hog1 and MAPKs in general regulate gene expression are not completely understood, although Hog1 can modify some transcription factors. Here we propose that Hog1 induces gene expression by a mechanism that involves recruiting a specific histone deacetylase complex to the promoters of genes regulated by osmostress. Cells lacking the Rpd3-Sin3 histone deac…