Search results for "MAPK"

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…

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-…

Show me your signaling– and I’ll tell you who you are

2009

See Article, pages 725–733Cancer research and therapy have come a long way:the field started out in search of a ‘‘magic bullet” accord-ing to Paul Ehrlich’s theory, and was hoping to identifya target which was pivotal to signaling survival in trans-formed cells. Indeed, certain diseases with monocausalmutations were identified, and targeting of the muta-tional products has helped in the design of treatmentstrategies. In chronic myeloid leukemia (CML), the con-stitutive activation of the tyrosine kinase BCR-ABL ispathognomonic [1], and multiple BCR-ABL kinaseinhibitors (e.g. imatinib mesylate, dasatinib, nilotinib)have been developed and successfully used in the treat-ment of CML offering near-…

A systems biology perspective on cholangiocellular carcinoma development: focus on MAPK-signaling and the extracellular environment.

2008

Background/Aims Multiple genes have been implicated in cholangiocellular carcinoma (CCC) development. However, the overall neoplastic risk is likely associated with a much lower number of critical physiological pathways. Methods To investigate this hypothesis, we extracted all published genetic associations for the development of CCC from PubMed (genetic association studies, but also studies associating genes and CCC in general, i.e. functional studies in cell lines, genetic studies in humans, knockout mice etc.) and integrated CCC microarray data. Results We demonstrated the MAPK pathway was consistently enriched in CCC. Comparing our data to genetic associations in HCC often successfully …

p38 MAPK activation is required for Paracentrotus lividus skeletogenesis

2008

We investigated the p38 MAPK role during sea urchin, Paracentrotus lividus, development. We found that at the morula stage, before the onset of skeletogenesis, p38 MAPK shows a peak of activity, and we tested whether p38 MAPK activity has any effect on skeletogenesis. By immunohistochemistry on whole-mount embryos we show the preferential localization of the active p38 form both in the presumptive PMCs and bilateral spiculo- genesis centers in control embryos, and in the radialized supernumerary spiculogenesis centers induced by NiCl2 treatment. By using SB203580, a p38 MAPK specific inhibitor, we show that p38 activity is required both for the initial triradiate spicule rudiments formation…

Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response

2013

Background Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post-radiogenic mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species (ROS) under irradiation (IR). Methods Intracellular ROS after IR were measured. We modeled radiation-induced ROS by exposure of two SCC lines to H2O2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA. Results We found eleva…

Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as par…

2010

Background. Irradiation plays a pivotal role in head and neck squamous cell carcinoma (HNSCC) treatment. However, especially recurrent tumors frequently show increased radioresistance. We analyzed irradiation-stimulated mitogen-activated protein kinase (MAPK) signaling pathways to define cellular rescue mechanisms. Methods. Irradiated HNSCC cells were screened for MAPK activation and results were confirmed and refined by functional analyses. Extracellular signal-regulated kinase (ERK) inhibitor U0126 application enabled us to specify postradiogenic cellu- lar responses. Vascular endothelial growth factor (VEGF) levels were analyzed additionally. Results. We observed a pronounced and time-de…

CIGARETTE SMOKE INDUCES p38 MAPK-INITIATED AND FAS-MEDIATED ERYPTOSIS

2022

Sources, Chemistry, and Biological Potential of Ellagitannins and Ellagic Acid Derivatives

2019

Abstract The consumption of polyphenols is considered an important part of a healthy life style and is related to reducing the risk for diseases. Ellagitanins (e.g., vescalagin, punicalagin, and castalagin) and ellagic acid and its derived compounds (e.g., urolithin) have been receiving attention in recent years as bioactive substances. This class of phenolic substances can be found in berries, pomegranates, walnuts, almonds, and other plant material that is consumed as traditional medicine to treat inflammatory diseases. Human gut microbiota are considered to play an important role in the bioactivity of ellagic acid derivative activity due to the production of urolithin and its antiinflamm…

p38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species

2013

p38 MAPKs are important mediators of signal transduction that respond to a wide range of extracellular stressors such as UV radiation, osmotic shock, hypoxia, pro-inflammatory cytokines, and oxidative stress. The most abundant family member is p38α, which helps to couple cell proliferation and growth in response to certain damaging stimuli. In fact, increased proliferation and impaired differentiation are hallmarks of p38α-deficient cells. It has been reported that reactive oxygen species (ROS) play a critical role in cytokine-induced p38α activation. Under physiological conditions, p38α can function as a mediator of ROS signaling and either activate or suppress cell cycle progression depen…