Search results for "Mitogen-activated protein"
showing 10 items of 353 documents
(+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury
2016
Abstract Background Sigma-1 receptors (σ 1 R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1 R agonist, in an in vitro model of microglia activation. Methods Microglia (BV2 cells) was exposed (3 h) to 1% oxygen and reoxygenation was allowed for 24 h. Cells were treated with different concentrations (1, 10, 25 and 50 μM) of (+)-pentazocine in the presence or absence of NE-100 (1 μM), a well established σ 1 R antagonist. Cell viability and apopto…
Activation of microglia synergistically enhances neurodegeneration caused by MPP+ in human SH-SY5Y cells
2019
While MPP+ may not directly activate microglia, the initial neuronal damage inflicted by the toxin may trigger microglia, possibly leading to synergistic pro-apoptotic interaction between neuro-inflammation and toxin-induced neurotoxicity, which may further aggravate neurodegeneration. However, what molecular targets are synergistically up or downregulated during this interaction is not well understood. Here, we addressed this by co-culturing fully differentiated human SH-SY5Y cells treated with parkinsonian toxin 1-Methyl-4-phenylpyridinium (MPP+), with endotoxin-activated microglial cell line EOC 20 to determine how this interaction affects pro-apoptotic (p38, JNK, and bax:bcl2 ratios) an…
Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p-ERK1/2 and Bax.
2018
Experimental studies have shown that overexpression of Rap guanine nucleotide exchange factor 1 (C3G) plays pro-survival and anti-apoptotic roles through molecule phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2) in cardiomyocytes. However, it is still unclear if silencing of C3G may increase cell survival inhibition and apoptosis in cardiomyocytes, and whether C3G silence induced injuries are reduced by the overexpression of C3G through regulation of p-ERK1/2 and pro-apoptotic molecule Bax. In this study, the rat-derived H9C2 cardiomyocytes were infected with C3G small hairpin RNA interference recombinant lentiviruses, which silenced the endogenous C3G expression in the ca…
Cytotoxicity ofSalvia miltiorrhizaAgainst Multidrug-Resistant Cancer Cells
2016
Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavag…
Fungicide resistance towards fludioxonil conferred by overexpression of the phosphatase gene Mo PTP 2 in Magnaporthe oryzae
2018
The fungicide fludioxonil causes hyperactivation of the Hog1p MAPK within the high-osmolarity glycerol signaling pathway essential for osmoregulation in pathogenic fungi. The molecular regulation of MoHog1p phosphorylation is not completely understood in pathogenic fungi. Thus, we identified and characterized the putative MoHog1p-interacting phosphatase gene MoPTP2 in the filamentous rice pathogen Magnaporthe oryzae. We found overexpression of MoPTP2 conferred fludioxonil resistance in M. oryzae, whereas the 'loss of function' mutant ΔMoptp2 was more susceptible toward the fungicide. Additionally, quantitative phosphoproteome profiling of MoHog1p phosphorylation revealed lower phosphorylati…
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells
2020
ObjectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.DesignA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional…
Inappropriate translation inhibition and P-body formation cause cold-sensitivity in tryptophan-auxotroph yeast mutants
2017
In response to different adverse conditions, most eukaryotic organisms, including Saccharomyces cerevisiae, downregulate protein synthesis through the phosphorylation of eIF2α (eukaryotic initiation factor 2α) by Gcn2, a highly conserved protein kinase. Gcn2 also controls the translation of Gcn4, a transcription factor involved in the induction of amino acid biosynthesis enzymes. Here, we have studied the functional role of Gcn2 and Gcn2-regulating proteins, in controlling translation during temperature downshifts of TRP1 and trp1 yeast cells. Our results suggest that neither cold-instigated amino acid limitation nor Gcn2 are involved in the translation suppression at low temperature. Howev…
The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at pr…
2015
The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression c…
In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment
2016
Abstract: An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expre…
The role of extracellular calcium in bone metastasis
2016
AbstractThis review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis.