Search results for "Mitogen-Activated Protein Kinase"
showing 10 items of 353 documents
Sea urchin deciliation induces thermoresistance and activates the p38 mitogen-activated protein kinase pathway.
2003
In this study, we demonstrate by a variety of approaches (ie, morphological analysis, Western blots, immunolocalization, and the use of specific antibodies) that hyperosmotic deciliation stress of sea urchin embryos induces a thermotolerant response. Deciliation is also able to activate a phosphorylation signaling cascade the effector of which might be the p38 stress-activated protein kinase because we found that the administration of the p38 inhibitor SB203580 to sea urchin deciliated gastrula embryos makes the hyperosmotic deciliation stress lethal.
Cabut, a C2H2 zinc finger transcription factor, is required during Drosophila dorsal closure downstream of JNK signaling.
2005
AbstractDuring dorsal closure, the lateral epithelia on each side of the embryo migrate dorsally over the amnioserosa and fuse at the dorsal midline. Detailed genetic studies have revealed that many molecules are involved in this epithelial sheet movement, either with a signaling function or as structural or motor components of the process. Here, we report the characterization of cabut (cbt), a new Drosophila gene involved in dorsal closure. cbt is expressed in the yolk sac nuclei and in the lateral epidermis. The Cbt protein contains three C2H2-type zinc fingers and a serine-rich domain, suggesting that it functions as a transcription factor. cbt mutants die as embryos with dorsal closure …
A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.
2012
In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
2021
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
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…
Integrin α2β1 Mediates Isoform-Specific Activation of p38 and Upregulation of Collagen Gene Transcription by a Mechanism Involving the α2 Cytoplasmic…
1999
Two collagen receptors, integrins alpha1beta1 and alpha2beta1, can regulate distinct functions in cells. Ligation of alpha1beta1, unlike alpha2beta1, has been shown to result in recruitment of Shc and activation of the Ras/ERK pathway. To identify the downstream signaling molecules activated by alpha2beta1 integrin, we have overexpressed wild-type alpha2, or chimeric alpha2 subunit with alpha1 integrin cytoplasmic domain in human osteosarcoma cells (Saos-2) lacking endogenous alpha2beta1. The chimeric alpha2/alpha1 chain formed a functional heterodimer with beta1. In contrast to alpha2/alpha1 chimera, forced expression of alpha2 integrin resulted in upregulation of alpha1 (I) collagen gene …
The endopolygalacturonase 1 from botrytis cinerea activates grapevine defense reactions unrelated to its enzyumatic activity
2003
A purified glycoprotein from Botrytis cinerea(strain T4), identified as endopolygalacturonase 1 (T4BcPG1) by mass spectrometry analysis, has been shown to activate defense reactions in grapevine (Vitis vinifera cv. Gamay). These reactions include calcium influx, production of active oxygen species, activation of two mitogen-activated protein kinases, defense gene transcript accumulation, and phytoalexin production. Most of these defense reactions were also activated in grapevine in response to purified oligogalacturonides (OGA) with a degree of polymerization of 9 to 20. In vivo, these active OGA might be a part of the released products resulting from endopolygalacturonase activity on plan…
Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity
2014
Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regul…
PET Imaging of the Impact of Extracellular pH and MAP Kinases on the p-Glycoprotein (Pgp) Activity
2012
The functional activity of p-glycoprotein (Pgp) can be increased in vitro by an extracellular acidosis via activation of MAP kinases (p38, ERK1/2). In order to study these effects in vivo a new (68)Ga-labeled PET tracer was developed which serves as a substrate of the Pgp and therefore indirectly mirrors the Pgp activity. For in vivo studies, experimental tumors were imaged under acidic conditions (inspiratory hypoxia, injection of lactic acid) and during inhibition of MAP kinases in a μ-PET system. In vitro, [(68)Ga]MFL6.MZ showed an accumulation within the cells of about 20% which was increased to 30% by Pgp inhibition. In solid tumors a marked tracer uptake was observed showing spatial h…
Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth
2017
C1q is the first recognition subcomponent of the complement classical pathway, which acts towards the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, including their involvement in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumour by encouraging their adhesion, migration and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of C1q in the microenvironment of malignant pleuric mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM…