Search results for "Signaling System"
showing 10 items of 105 documents
Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke
2018
Abstract Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after…
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.
2018
See Contreras and Hippenmeyer (doi:10.1093/brain/awy218) for a scientific commentary on this article. Autism spectrum disorders (ASDs) are complex conditions with diverse aetiologies. Szczurkowska et al. demonstrate that two ASD-related molecules – FGFR2 and Negr1 – physically interact to act on the same downstream pathway, and regulate cortical development and ASD-relevant behaviours in mice. Identifying common mechanisms in ASDs may reveal targets for pharmacological intervention.
The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis
2017
Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity …
DNA methylomes reveal biological networks involved in human eye development, functions and associated disorders
2017
This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are…
JNK pathway and heat shock response mediate the survival of C26 colon carcinoma bearing mice fed with the mushroom Pleurotus eryngii var. eryngii wit…
2021
In the last few years, there has been emerging interest in developing treatments against human diseases using natural bioactive content. Here, the powder of the edible mushroom Pleurotus eryngii var. eryngii was mixed with the normal diet of mice bearing C26 colon carcinoma. Interestingly, it was evidenced by a significant increase in the survival rate of C26 tumor-bearing mice accompanied by a significant increase in Hsp90 and Hsp27 protein levels in the tumors. These data were paralleled by a decrease in Hsp60 levels. The mushroom introduced in the diet induced the inhibition of the transcription of the pro-inflammatory cytokines IL-6 and IL-1 exerting an anti-inflammatory action. The eff…
ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans
2016
Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca2+ signaling via opening of the calcium-homeostasis modulator-1 (CALHM1) channel. Furthermore, f…
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma
2020
High-risk 11q deleted neuroblastomas typically display undifferentiated/poorly differentiated morphology. Neuroblastoma is thought to develop from Schwann cell precursors and undifferentiated neural crest (NC) derived cells. It is therefore vital to understand mechanisms involved in the block of differentiation. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in maintenance of undifferentiated NC-derived progenitors via repression of DLG2, a tumor suppressor in neuroblastoma. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors become chromaffin cells of the adrenal gland. We …
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…
TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
2017
We previously showed that thyrotropin (TSH)/insulinlike growth factor (IGF)-1 receptor cross-talk appears to be involved in Graves’ orbitopathy (GO) pathogenesis and upregulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients, coadministration of TSH and IGF-1 induces synergistic increases in hyaluronan secretion. In human thyrocytes, TSH plus IGF-1 synergistically increased expression of the sodium-iodide symporter that appeared to involve ERK1/2 activation. However, the details of ERK1/2 activation were not known, nor was whether ERK1/2 was involved in this synergism in other cell types. Using primary cultures of GO fibroblasts (GOFs) and human thyr…
Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training
2014
This study investigated the effects of vitamin C and E supplementation on acute responses and adaptations to strength training. Thirty-two recreationally strength-trained men and women were randomly allocated to receive a vitamin C and E supplement (1000 mg day(-1) and 235 mg day(-1), respectively), or a placebo, for 10 weeks. During this period the participants' training involved heavy-load resistance exercise four times per week. Muscle biopsies from m. vastus lateralis were collected, and 1 repetition maximum (1RM) and maximal isometric voluntary contraction force, body composition (dual-energy X-ray absorptiometry), and muscle cross-sectional area (magnetic resonance imaging) were measu…