Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval.
View Article and Find Full Text PDFFront Oncol
January 2024
Background: Advances in the understanding of the pathobiology of childhood B-cell acute lymphoblastic leukemia (B-ALL) have led towards risk-oriented treatment regimens and markedly improved survival rates. However, treatment-related toxicities remain a major cause of mortality in developing countries. One of the most common adverse effects of chemotherapy in B-ALL is the hematologic toxicity, which may be related to genetic variants in membrane transporters that are critical for drug absorption, distribution, and elimination.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
June 2024
Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment.
View Article and Find Full Text PDFHypertension is a multifactorial disease characterized by vascular and renal dysfunction, cardiovascular remodeling, inflammation, and fibrosis, all of which are associated with oxidative stress. We previously demonstrated cellular reactive oxygen species (ROS) imbalances may impact the structural and biochemical functions of blood cells and reported downregulation of β-dystroglycan (β-Dg) and overexpression of the epithelial sodium channel (ENaC) contribute to the pathophysiology of hypertension. In this study, we aimed to determine the expression of dystroglycans (Dg) and ENaC in platelet progenitors (megakaryocytes) and their surrounding niches.
View Article and Find Full Text PDFThe establishment of persistent dengue virus infection within the cells of the mosquito vector is an essential requirement for viral transmission to a new human host. The mechanisms involved in the establishment and maintenance of persistent infection are not well understood, but it has been suggested that both viral and cellular factors might play an important role. In the present work, we evaluated differential gene expression in cells acutely (C6/36-HT) and persistently infected (C6-L) with Dengue virus 2 by cDNA-AFLP.
View Article and Find Full Text PDFHypertension (HTN) causes end-organ damage and is a major cause of morbidity and mortality globally. Recent studies suggested blood cells participate in the maintenance of HTN. Platelets-anucleated cell fragments derived from megakaryocytes-exert diverse functions, including their well-characterized role in the formation of hemostatic clots.
View Article and Find Full Text PDFCellular heterogeneity and diversity are recognized to contribute to the functions of neutrophils under homeostatic and pathological conditions. We previously suggested that the chronic inflammatory responses associated with hypertension (HTN) are related to the participation of different subpopulations of neutrophils. Two populations of neutrophils can be obtained by density gradient centrifugation: normal-density neutrophils (NDN) and low-density neutrophils (LDN).
View Article and Find Full Text PDFPlatelet lysate has attracted attention for different biomedical applications, including biological processes where cellular proliferation and migration have been altered. Spectroscopic properties of a platelet lysate obtained from human platelets were performed in order to be incorporated in polymeric nanoparticles and then into a Pluronic F127 hydrogel, intended for wound healing (more details can be found at https://doi.org/10.
View Article and Find Full Text PDFArterial hypertension (HTN) is a world health concern presenting difficulties for its early detection. It leads to cardiovascular and kidney complications that increase morbidity in adults. Overexpression in the epithelial sodium channel (ENaC) in membrane platelets can be related with the presence of HTN and thus can be used as a biomarker to detect this medical condition.
View Article and Find Full Text PDFA thermo-responsive hydrogel of Pluronic F-127, containing PLGA nanoparticles loaded with a platelet lysate for wound treatment, was prepared. A high rate of incorporation of the lysate (about 80%) in the nanoparticles was achieved by the double emulsion-solvent evaporation method. The nanoparticles were characterized by measuring their size (about 318 nm), polydispersity index (0.
View Article and Find Full Text PDFExp Cell Res
December 2019
Arterial hypertension (HTN) can lead to serious organ damage. Several mechanisms have been implicated in the pathogenesis of HTN including constitutive activation of platelets, which increases the risk of aggregation and clot formation. We recently demonstrated the plasma membranes of platelets from patients with HTN exhibit modified structural and physicochemical properties; Raman and Fourier transform infrared by attenuated total reflectance (FTIR-ATR) spectroscopy also indicated lipid content and protein structure alterations.
View Article and Find Full Text PDFGenetic and environmental factors may contribute to high blood pressure, which is termed essential hypertension. Hypertension is a major independent risk factor for cardiovascular disease, stroke and renal failure; thus, elucidation of the etiopathology of hypertension merits further research. We recently reported that the platelets and neutrophils of patients with hypertension exhibit altered biophysical characteristics.
View Article and Find Full Text PDFThe α-Dystrobrevin gene encodes at least five different protein isoforms, expressed in diverse tissues. The α-Dystrobrevin-1 isoform (α-Db-1) is a member of the cytoplasmic dystrophin-associated protein complex, which has a C-terminal extension comprising at least three tyrosine residues susceptible to phosphorylation in vivo. We previously described α-Db in stem-progenitor cells and blood neutrophils as playing a scaffolding role and, in association with kinesin and microtubules, α-Db promotes platelet-granule trafficking.
View Article and Find Full Text PDFAims: Previous reports have demonstrated that alterations or reduced expression of Dystroglycan (Dg) complex (αDg and βDg subunits) are related to progression and severity of neoplastic solid tissues. Therefore we determined the expression pattern and subcellular distribution of Dg complex in Acute Myeloid Leukemia (AML) primary blasts (M1, M2, and M3 phenotypes), as well as HL-60 and Kasumi-1 leukemia cell lines. Additionally, we evaluated the relative expression of the main enzymes controlling α-Dg glycosylation to ascertain the post-translational modifications in the leukemia cell phenotype.
View Article and Find Full Text PDFPlatelets are the most prominent elements of blood tissue involved in hemostasis at sites of blood vessel injury. Platelet cytoskeleton is responsible for their shape modifications observed during activation and adhesion to the substratum; therefore the interactions between cytoskeleton and plasma membrane are critical to modulate blood platelet functions. Several cytoskeletal components and binding partners, as well as enzymes that regulate the cytoskeleton, localize to membrane/lipid rafts (MLR) and regulate lateral diffusion of membrane proteins and lipids.
View Article and Find Full Text PDFDystroglycan has recently been characterized in blood tissue cells, as part of the dystrophin glycoprotein complex but to date nothing is known of its role in the differentiation process of neutrophils. We have investigated the role of dystroglycan in the human promyelocytic leukemic cell line HL-60 differentiated to neutrophils. Depletion of dystroglycan by RNAi resulted in altered morphology and reduced properties of differentiated HL-60 cells, including chemotaxis, respiratory burst, phagocytic activities and expression of markers of differentiation.
View Article and Find Full Text PDFActivated platelets adhere to the exposed subendothelial extracellular matrix and undergo a rapid cytoskeletal rearrangement resulting in shape change and release of their intracellular dense and alpha granule contents to avoid hemorrhage. A central step in this process is the elevation of the intracellular Ca(2+) concentration through its release from intracellular stores and on throughout its influx from the extracellular space. The Epithelial sodium channel (ENaC) is a highly selective Na(+) channel involved in mechanosensation, nociception, fluid volume homeostasis, and control of arterial blood pressure.
View Article and Find Full Text PDFUpon vascular injury, platelets adhere to the exposed extracellular matrix, which triggers the platelet activation and aggregation to form a hemostatic plug to seal the wound. All of these events involve dramatic changes in shape because of the cytoskeleton reorganization. The versatility of the cytoskeleton's main elements depends on the biochemical nature of the elements, as well as on the associated proteins that confer multiple functions within the cell.
View Article and Find Full Text PDFThe role of platelets in coagulation and the haemostatic process was initially suggested two centuries ago, and under appropriate physiological stimuli, these undergo abrupt morphological changes, attaching and spreading on damaged endothelium, preventing bleeding. During the adhesion process, platelet cytoskeleton reorganizes generating compartments in which actin filaments, microtubules, and associated proteins are arranged in characteristic patterns mediating crucial events, such as centralization of their organelles, secretion of granule contents, aggregation with one another to form a haemostatic plug, and retraction of these aggregates. However, the role of Intermediate filaments during the platelet adhesion process has not been explored.
View Article and Find Full Text PDFCatSper channels are essential for hyperactivity of sperm flagellum, progesterone-mediated chemotaxis and oocyte fertilization. Catsper genes are exclusively expressed in the testis during spermatogenesis, but the function and regulation of the corresponding promoter regions are unknown. Here, we report the cloning and characterization of the promoter regions in the human and murine Catsper1 genes.
View Article and Find Full Text PDFHematopoietic stem cells (HSC) are defined by their cardinal properties, such as sustained proliferation, multilineage differentiation, and self-renewal, which give rise to a hierarchy of progenitor populations with more restricted potential lineage, ultimately leading to the production of all types of mature blood cells. HSC are anchored by cell adhesion molecules to their specific microenvironment, thus regulating their cell cycle, while cell migration is essentially required for seeding the HSC of the fetal bone marrow (BM) during development as well as in adult BM homeostasis. The dystrophin-associated protein complex (DAPC) is a large group of membrane-associated proteins linking the cytoskeleton to the extracellular matrix and exhibiting scaffolding, adhesion, and signaling roles in muscle and non-muscle cells including mature blood cells.
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