Search results for "MAPK"
showing 10 items of 238 documents
“Cysteinyl leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to signal transducer and activator of transcription 1-me…
2008
Abstract We studied the effect of leukotriene D(4) (LTD(4)) on a human bronchial epithelial cell line (16HBE) overexpressing the cysteinyl leukotriene (CysLT) (1) receptor (HBECysLT(1)R), looking at the associated signal transduction mechanisms as well as at effects on inflammatory cell adhesion. The results obtained showed that LTD(4) increases the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 and of the signal transducer and activator of transcription 1 (STAT-1) in serine 727 (STAT-1Ser727), resulting in increased eosinophil adhesion to HBECysLT(1)R, associated with enhanced surface expression of intercellular adhesion molecule (ICAM) 1. Pretreatment with a Cy…
How DNA lesions are turned into powerful killing structures: Insights from UV-induced apoptosis
2008
Mammalian cells treated with ultraviolet (UV) light provide one of the best-known experimental systems for depicting the biological consequences of DNA damage. UV irradiation induces the formation of DNA photoproducts, mainly cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts [(6-4)PPs], that drastically impairs DNA metabolism, culminating in the induction of cell death by apoptosis. While CPDs are the most important apoptosis-inducing lesions in DNA repair proficient cells, recent data indicates that (6-4)PPs also signals for apoptosis in DNA repair deficient cells. The toxic effects of these unrepaired DNA lesions are commonly associated with transcription …
Tributyltin chloride-induced effects on protein tyrosine phosphorylation and on extracellular-signal-regulated kinase (ERK) phosphorilation in Ascidi…
2011
Ascidians represent an intriguing candidate experimental system for studying the effects of environmental stress. We studied TBT effects and probable related pathways were investigated on ascidian embryos by using Western immunoblotting. Among the various signal transduction pathways involved in response to environmental stress, both tyrosine kinase signalling and MAPKs have been played a significant role. To better understand molecular mechanisms after exposure to TBT we studied the two signal transduction pathways above mentioned. Attempting to unravel the molecular effects of TBT-induced on ascidians embryogenesis, TBT treatments carried out in Phallusia mammillata embryos at gastrula st…
Effects of tributyltin chloride in ascidian embryos: modulation of kinase-mediated signalling pathways
2009
We studied the effects of various TBT concentrations by assaying the activity of ERK 1/2 (p44/42) and phospho-ERK1/2 (phospho-p44/42), proteins with a key role in ascidian development, and tyrosine kinase-dependent pathway. The effects of this xenobiotic and the role of some signalling mechanisms on ascidian embryos were examined by using Western immunoblotting. The tyrosine phosphorylation pattern in the ascidians Ciona intestinalis and Phallusia mammillata development was examined and different levels of protein phosphorylation were found as a response to TBT at μM range. To determine whether another key signalling pathway was activated, the effects of TBT on the phosphorylation state of …
Early asymmetric cues triggering the dorsal/ventral gene regulatory network of the sea urchin embryo
2014
Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-containing repressor is expressed by prospective dorsal cells, spatially facing and preceding the onset of nodal transcription. We report that Hbox12 misexpression provokes DV abnormalities, attenuating nodal and nodal-dependent transcription. Reciprocally, impairing hbox12 function disrupts DV polarity by allowing ectopic expression of nodal. Clonal loss-of-function, inflicted by b…
Distribución, función y vías de señalización de los adrenoceptores β a nivel vascular
2014
Se ha analizado la contribución de los diferentes subtipos de adrenoceptores (AR) β (β1, β2 β3) en la vasodilatación, determinando su localización en las diferentes células vasculares y evaluando la implicación de las vías de señalización adenilato ciclasa (AC)/AMPc/PKA y/o NO/guanilato ciclasa soluble (GCs)/GMPc, en dos lechos vasculares representantes de: los vasos de resistencia, como la arteria mesentérica de resistencia (A.M.R.) de rata, y de conductancia, como la aorta de rata. Los resultados obtenidos muestran que, a pesar de que los tres subtipos de AR β se expresan en ambos vasos, su participación en la respuesta funcional, así como la vía de señalización utilizada, es diferente se…
Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis
2018
Psoriatic plaques tend to localize to the knees and elbows, areas that are particularly subject to mechanical stress resulting from bending and friction. Moreover, plaques often develop at sites of mechanical trauma or injury (Koebner phenomenon). Nevertheless, mechanotransduction has never been linked to psoriasis. Polycystins (polycystin-1, PC1; polycystin-2, PC2) are mechanosensitive molecules that function as key regulators of cellular mechanosensitivity and mechanotransduction. The aim of this in vitro study was to investigate the role of polycystins in the development of psoriasis. We showed that PC1 knockdown in HaCaT cells led to an elevated mRNA expression of psoriasis-related biom…
Non-small cell lung cancer (NSCLC), EGFR downstream pathway activation and TKI targeted therapies sensitivity: Effect of the plasma membrane-associat…
2017
Adenocarcinoma of Non-Small Cell Lung Cancer (NSCLC) is a severe disease. Patients carrying EGFR mutations may benefit from EGFR targeted therapies (e.g.: gefitinib). Recently, it has been shown that sialidase NEU3 directly interacts and regulates EGFR. In this work, we investigate the effect of sialidase NEU3 overexpression on EGFR pathways activation and EGFR targeted therapies sensitivity, in a series of lung cancer cell lines. NEU3 overexpression, forced after transfection, does not affect NSCLC cell viability. We demonstrate that NEU3 overexpression stimulates the ERK pathway but this activation is completely abolished by gefitinib treatment. The Akt pathway is also hyper-activated upo…
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
2019
Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called a…
The Friedreich's Ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals
2010
DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron–sulfur clusters). The nuclearencoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte-specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frata…