Search results for "ERK1"
showing 10 items of 17 documents
Characteristic ERK1/2 signaling dynamics distinguishes necroptosis from apoptosis
2021
International audience; ERK1/2 involvement in cell death remains unclear, although many studies have demonstrated the importance of ERK1/2 dynamics in determining cellular re- sponses. To untangle how ERK1/2 contributes to two cell death programs, we investigated ERK1/2 signaling dynamics during hFasL-induced apoptosis and TNF-induced necroptosis in L929 cells. We observed that ERK1/2 inhibition sensi- tizes cells to apoptosis while delaying necroptosis. By monitoring ERK1/2 activity by live-cell imaging using an improved ERK1/2 biosensor (EKAR4.0), we reported differential ERK1/2 signaling dynamics between cell survival, apoptosis, and nec- roptosis. We also decrypted a temporally shifted …
Intestinal CD36 : A long chain fatty acid receptor which controls post prandial hypertriglyceridemia, endotoxemia and intestinal epithelium integrity
2014
Post prandial hypertriglyceridemia represents a risk factor for cardio-vascular diseases and it is associated with metabolic syndrom, obesity, and insulino-resistance. The intestine influences lipid bioavailibility and post prandial hypertriglyceridemia. It controls the quantity and the quality of secreted chylomicrons by adapting its metabolism according to the lipid content of the diet. Nevertheless, the mechanism of dietary lipid detection by the enterocyte is not understood. Our work demonstrates that the transmembrane glycoprotein CD36 is a Long Chain Fatty Acid (LCFA) receptor which triggers ERK1/2 activation. This activation is responsible for the induction of mRNA rate of 3 key prot…
Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p-ERK1/2 and Bax
2019
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…
Trastuzumab therapy vs tetracycline controlled ERBB2 downregulation: influence on tumour development in an ERBB2-dependent mouse tumour model
2008
Trastuzumab (Herceptin) has improved therapy of breast cancer. Only patients overexpressing ERBB2 are treated with trastuzumab, whereas its use in tumours without ERBB2 expression is useless. This led to the concept that the subgroup of trastuzumab-sensitive tumours is ‘ERBB2-dependent', meaning that ERBB2 signalling is indispensable for growth of these tumours. We used a mouse model that allows anhydrotetracycline (ATc)-controlled downregulation of ERBB2 in tumour tissue. ERBB2 mRNA and protein expression were downregulated below detection limit leading to a macroscopically complete tumour remission within 14 days. Tumour remission was accompanied by a strong decrease in proliferation, a m…
Biphasic Erk1/2 activation sequentially involving Gs and Gi signaling is required in beta3-adrenergic receptor-induced primary smooth muscle cell pro…
2013
Abstract The beta3 adrenergic receptor (B3-AR) reportedly induces cell proliferation, but the signaling pathways that were proposed, involving either Gs or Gi coupling, remain controversial. To further investigate the role of G protein coupling in B3-AR induced proliferation, we stimulated primary human myometrial smooth muscle cells with SAR150640 (B3-AR agonist) in the absence or presence of variable G-protein inhibitors. Specific B3-AR stimulation led to an Erk1/2 induced proliferation. We observed that the proliferative effects of B3-AR require two Erk1/2 activation peaks (the first after 3 min, the second at 8 h). Erk1/2 activation at 3 min was mimicked by forskolin (adenylyl-cyclase a…
HSP60 activity on human bronchial epithelial cells
2017
HSP60 has been implicated in chronic inflammatory disease pathogenesis, including chronic obstructive pulmonary disease (COPD), but the mechanisms by which this chaperonin would act are poorly understood. A number of studies suggest a role for extracellular HSP60, since it can be secreted from cells and bind Toll-like receptors; however, the effects of this stimulation have never been extensively studied. We investigated the effects (pro- or anti-inflammatory) of HSP60 in human bronchial epithelial cells (16-HBE) alone and in comparison with oxidative, inflammatory, or bacterial challenges. 16-HBE cells were cultured for 1–4 h in the absence or presence of HSP60, H2O2, lipopolysaccharide (…
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
Identification et caractérisation du récepteur à la flagelline (VvFLS2) et recherche du récepteur aux chito-oligosaccharides chez la vigne
2014
Pattern-recognition receptors (PRRs) play a key role in plant immunity by assuring recognition of microbe-associated molecular patterns (MAMPs), signature of microbial presence. MAMP perception constitutes the first layer of pathogen detection and activates defense mechanisms that aim to block the intruder. This study brings an insight into how grapevine (Vitis vinifera) perceives two MAMPs: the flagellin-derived flg22 peptide and chitin, which are conserved motifs occurring over the whole bacterial and fungal classes, respectively. This study analyzed MAMP-triggered early signaling events, defense gene expression and also the efficiency of elicited defense against gray mold and downy milde…
The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer
2018
Background CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. Methods The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRβ was e…
mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Er…
2011
In the present study we aimed to verify if the enhancement of glial cell line-derived neurotrophic factor (GDNF) production in mouse striatum following treatment with LY379268 may also induce in the nigrostriatal system a time-related activation of RET receptor and its specific intracellular signaling. For this purpose, we have investigated the effects of LY379268 treatment on RET phosphorylation at the Tyr1062 and on downstream signaling Erk1/2, Akt and PLCγ1 pathway activation. The results showed that treatment with LY379268 (3 mg/kg) induces a significant increase of GDNF levels and time-related RET and Erk1/2 phosphorylation in the striatum. These increases were detected at 24 h and 48 …