Search results for " MAPK"
showing 10 items of 27 documents
Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis
2022
Eryptosis is a physiological mechanism for the clearance of senescent or damaged erythrocytes by phagocytes. Excessive eryptosis is stimulated under several pathologies and associated with endothelial injury and thrombosis. Cigarette smoke (CS) is an established risk factor for vascular diseases and cigarette smokers have high-levels of eryptotic erythrocytes. This study, for the first time, investigates the mechanism by which CS damages red blood cells (RBCs). CS extract (CSE) from commercial cigarettes was prepared and standardized for nicotine content. Cytofluorimetric analysis demonstrated that treatment of human RBCs with CSE caused dose-dependent, phosphatidylserine externalization an…
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…
Effects of two organotin(IV)(sulfonato phenyl)porphynates on the MAPKs and on the growth of A375 human melanoma cells
2009
Previously we showed apoptotic induction in A375 human melanoma cells using two complexes of the meso-tetra(4-sulfonatophenyl)porphinate (TPPS), (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS. To understand how these compounds activate apoptosis in melanoma cells we studied MAPKs and the (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS cellular uptake. Western blotting experiments showed activated protein kinases ERK 1/2, JNK and p38 in 10 μM (Bu 2 Sn) 2 TPPS- and 1 μM (Bu 3 Sn) 4 TPPS-treated melanoma cells, which suggests that the three MAP kinases are involved in the apoptotic death of A375-treated cells. By taking advantage of the porphyrin fluorescence, we found a fast concentration of (Bu 2 Sn) 2 TPPS an…
Manganese overload affects p38 MAPK phosphorylation and metalloproteinase activity during sea urchin embryonic development.
2014
Abstract In the marine environment, manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. In earlier reports we found that the exposure of Paracentrotus lividus sea urchin embryos to manganese produced phenotypes with no skeleton. In addition, manganese interfered with calcium uptake, perturbed extracellular signal-regulated kinase (ERK) signaling, affected the expression of skeletogenic genes, and caused an increase of the hsc70 and hsc60 protein levels. Here, we extended our studies focusing on the temporal activation of the p38 mitogen-activated protein kinase (p38 MAPK) and the proteolytic activity of metalloprot…
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
2017
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) partici…
Polymorphisms within the TNFSF4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the cont…
2020
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a twostage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungi…
Redox signaling in acute pancreatitis
2015
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…
L-selectin regulates human neutrophil transendothelial migration
2021
ABSTRACT The migration of circulating neutrophils towards damaged or infected tissue is absolutely critical to the inflammatory response. L-selectin is a cell adhesion molecule abundantly expressed on circulating neutrophils. For over two decades, neutrophil L-selectin has been assigned the exclusive role of supporting tethering and rolling – the initial stages of the multi-step adhesion cascade. Here, we provide direct evidence for L-selectin contributing to neutrophil transendothelial migration (TEM). We show that L-selectin co-clusters with PECAM-1 – a well-characterised cell adhesion molecule involved in regulating neutrophil TEM. This co-clustering behaviour occurs specifically during …
Phospho-p38 MAPK expression in COPD patients and asthmatics and in challenged bronchial epithelium
2015
<b><i>Background:</i></b> The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. <b><i>Objectives:</i></b> To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. <b><i>Methods:</i></b> Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in pat…
Symmetry Breaking and Establishment of Dorsal/Ventral Polarity in the Early Sea Urchin Embryo
2015
The mechanisms imposing the Dorsal/Ventral (DV) polarity of the early sea urchin embryo consist of a combination of inherited maternal information and inductive interactions among blastomeres. Old and recent studies suggest that a key molecular landmark of DV polarization is the expression of nodal on the future ventral side, in apparent contrast with other metazoan embryos, where nodal is expressed dorsally. A subtle maternally-inherited redox anisotropy, plus some maternal factors such as SoxB1, Univin, and p38-MAPK have been identified as inputs driving the spatially asymmetric transcription of nodal. However, all the mentioned factors are broadly distributed in the embryo as early as no…