Acanthocyte

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Adrian Danek - One of the best experts on this subject based on the ideXlab platform.

  • the erythrocyte sedimentation rate and its relation to cell shape and rigidity of red blood cells from chorea acanthocytosis patients in an off label treatment with dasatinib
    Biomolecules, 2021
    Co-Authors: Antonia Rabe, Kevin Peikert, Alexis Darras, Greta Simionato, Anil K Dasanna, Jurgen Geisel, Alexander Kihm, Hannes Glas, Stephan Quint, Adrian Danek
    Abstract:

    Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called Acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the Acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of Acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.

  • current state of knowledge in chorea acanthocytosis as core neuroacanthocytosis syndrome
    European Journal of Medical Genetics, 2017
    Co-Authors: Kevin Peikert, Adrian Danek, Andreas Hermann
    Abstract:

    Abstract Neuroacanthocytosis (NA) syndromes are a group of rare diseases characterized by neurological disorders and misshaped spiky red blood cells (Acanthocytes) including Chorea-Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington disease-like 2 (HDL 2), pantothenate kinase-associated neurodegeneration (PKAN), abeta- and hypobetalipoproteinemia and aceruloplasminemia. This clinically and genetically heterogeneous group of diseases shares main clinical features presenting most often as a hyperkinetic movement disorder. Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms. The current review focuses upon ChAc as the core entity of NA syndromes caused by mutations in the VPS13A gene. The support of patient organizations and the ERA-NET initiative yielded to different multidisciplinary efforts with significant progress on our understanding of ChAc. Disturbances in two pathways are currently considered to be significantly involved in the pathophysiology of ChAc, namely elevated Lyn kinase phosphorylation and decreased signaling via Phosphoinositide 3-kinase (PI3K). These recent developments may reveal potential drugable targets for causative therapies of ChAc.

  • identification of phospho-tyrosine sub-networks related to Acanthocyte generation in neuroacanthocytosis. PLoS One 2012
    2016
    Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela Siciliano
    Abstract:

    Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of Acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of Acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b

  • Alterations of Red Cell Membrane Properties in
    2016
    Co-Authors: Claudia Siegl, Benedikt Bader, Adrian Danek, Patricia Hamminger, Herbert Jank, Uwe Ahting, Allison Gregory, Monika Hartig, Susan Hayflick, Andreas Hermann
    Abstract:

    Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA Acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasm

  • Computational Identification of Phospho-Tyrosine Sub- Networks Related to Acanthocyte Generation in
    2016
    Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela Siciliano
    Abstract:

    Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of Acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of Acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b

Lucia De Franceschi - One of the best experts on this subject based on the ideXlab platform.

  • identification of phospho-tyrosine sub-networks related to Acanthocyte generation in neuroacanthocytosis. PLoS One 2012
    2016
    Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela Siciliano
    Abstract:

    Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of Acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of Acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b

  • Computational Identification of Phospho-Tyrosine Sub- Networks Related to Acanthocyte Generation in
    2016
    Co-Authors: Lucia De Franceschi, Benedikt Bader, Adrian Danek, Ruth H. Walker, Hans H Jung, Maria Teresa Dotti, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela Siciliano
    Abstract:

    Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of Acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of Acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks b

  • Pedigree and RBC morphology of the subjects in this study.
    2015
    Co-Authors: Judith C. A. Cluitmans, Lucia De Franceschi, Carlo Tomelleri, Zuhal Yapici, Sip Dinkla, Petra Bovee-geurts, Venkatachalam Chokkalingam, Roland Brock, Giel J. G. C. M. Bosman
    Abstract:

    (A) Patients who are clinically diagnosed with PKAN are indicated in black, the healthy relatives are indicated in white. (B) Representative pictures of blood films used for classification of cell shape. (C) Cells are classified in discocyte, echinocyte, Acanthocyte or otherwise misshapen. The graph depicts the percentages of different cell morphologies in PKAN patients (marked with an asterisk) and their unaffected family members, compared to healthy donors (control 1+2) (see also S1 Fig for other PKAN families).

  • Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes.
    Current opinion in hematology, 2014
    Co-Authors: Lucia De Franceschi, Giel J. C. G. M. Bosman, Narla Mohandas
    Abstract:

    PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as Acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). RECENT FINDINGS: Although molecular defects associated with neuroacanthocytosis have been identified recently, their pathophysiology and the related RBC abnormalities are largely unknown. Studies in ChAc RBCs have shown an altered association between the cytoskeleton and the integral membrane protein compartment in the absence of major changes in RBC membrane composition. In ChAc RBCs, abnormal Lyn kinase activation in a Syk-independent fashion has been reported recently, resulting in increased band 3 tyrosine phosphorylation and perturbation of the stability of the multiprotein band 3-based complexes bridging the membrane to the spectrin-based membrane skeleton. Similarly, in MLS, the absence of XK-protein, which is associated with the spectrin-actin-4.1 junctional complex, is associated with an abnormal membrane protein phosphorylation state, with destabilization of the membrane skeletal network resulting in generation of Acanthocytes. SUMMARY: A novel mechanism in generation of Acanthocytes involving abnormal Lyn activation, identified in ChAc, expands the acanthocytosis phenomenon toward protein-protein interactions, controlled by phosphorylation-related abnormal signaling.

  • Computational Identification of Phospho-Tyrosine Sub-Networks Related to Acanthocyte Generation in Neuroacanthocytosis
    PloS one, 2012
    Co-Authors: Lucia De Franceschi, Giovanni Scardoni, Carlo Tomelleri, Sara Mazzucco, Angela Siciliano
    Abstract:

    Acanthocytes, abnormal thorny red blood cells (RBC), are one of the biological hallmarks of neuroacanthocytosis syndromes (NA), a group of rare hereditary neurodegenerative disorders. Since RBCs are easily accessible, the study of Acanthocytes in NA may provide insights into potential mechanisms of neurodegeneration. Previous studies have shown that changes in RBC membrane protein phosphorylation state affect RBC membrane mechanical stability and morphology. Here, we coupled tyrosine-phosphoproteomic analysis to topological network analysis. We aimed to predict signaling sub-networks possibly involved in the generation of Acanthocytes in patients affected by the two core NA disorders, namely McLeod syndrome (MLS, XK-related, Xk protein) and chorea-acanthocytosis (ChAc, VPS13A-related, chorein protein). The experimentally determined phosphoproteomic data-sets allowed us to relate the subsequent network analysis to the pathogenetic background. To reduce the network complexity, we combined several algorithms of topological network analysis including cluster determination by shortest path analysis, protein categorization based on centrality indexes, along with annotation-based node filtering. We first identified XK- and VPS13A-related protein-protein interaction networks by identifying all the interactomic shortest paths linking Xk and chorein to the corresponding set of proteins whose tyrosine phosphorylation was altered in patients. These networks include the most likely paths of functional influence of Xk and chorein on phosphorylated proteins. We further refined the analysis by extracting restricted sets of highly interacting signaling proteins representing a common molecular background bridging the generation of Acanthocytes in MLS and ChAc. The final analysis pointed to a novel, very restricted, signaling module of 14 highly interconnected kinases, whose alteration is possibly involved in generation of Acanthocytes in MLS and ChAc.

Hiroshi Mitani - One of the best experts on this subject based on the ideXlab platform.

  • sensitivity of medaka oryzias latipes to 4 nonylphenol subacute exposure erythrocyte alterations and apoptosis
    Environmental Toxicology and Pharmacology, 2018
    Co-Authors: Alaa Eldin H Sayed, Shoji Oda, Chisato Kataoka, Shosaku Kashiwada, Hiroshi Mitani
    Abstract:

    Abstract The present study was undertaken to assess the effects of the endocrine-disrupting compound; 4-nonylphenol (4-NP) in medaka (Oryzias latipes). The frequencies of erythrocyte alterations, apoptosis, and micronuclei were used as biological indicators of damage. Medaka were exposed 15 days to 4-NP at three sublethal concentrations (50, 80, and 100 μg/l 4-NP) and results compared with those of a previous study using catfish as an animal model. Exposure of medaka resulted in a dose-dependent increase in the frequency of erythrocyte alterations, apoptosis and micronucleus (MN). Many morphological alterations and nuclear abnormalities were observed, including Acanthocytes, lobed nucleus, eccentric nucleus, fragmented nucleus, blebbed nucleus, binuclei, deformed nucleus, notched nucleus, hemolysed cells, crenated cells, teardrop-like cells, and schistocytes. Mortality was recorded after treatment with 80 and 100 μg/l 4-NP, indicating that medaka are more sensitive than catfish to 4-NP exposure. We concluded that, 4-NP causes several malformations in the shape and number of erythrocytes in medaka, indicating its genotoxicity.

  • apoptosis and morphological alterations after uva irradiation in red blood cells of p53 deficient japanese medaka oryzias latipes
    Journal of Photochemistry and Photobiology B-biology, 2016
    Co-Authors: Alla Eldin Hamid Sayed, Tomomi Watanabeasaka, Shoji Oda, Hiroshi Mitani
    Abstract:

    Morphological alterations in red blood cells were described as hematological bioindicators of UVA exposure to investigate the sensitivity to UVA in wild type Japanese medaka (Oryzias latipes) and a p53 deficient mutant. The fewer abnormal red blood cells were observed in the p53 mutant fish under the control conditions. After exposure to different doses of UVA radiation (15min, 30min and 60min/day for 3days), cellular and nuclear alterations in red blood cells were analyzed in the UVA exposed fish compared with non-exposed controls and those alterations included Acanthocytes, cell membrane lysis, swollen cells, teardrop-like cell, hemolyzed cells and sickle cells. Those alterations were increased after the UVA exposure both in wild type and the p53 deficient fish. Moreover, apoptosis analyzed by acridine orange assay showed increased number of apoptosis in red blood cells at the higher UVA exposure dose. No micronuclei but nuclear abnormalities as eccentric nucleus, nuclear budding, deformed nucleus, and bilobed nucleus were observed in each group. These results suggested that UVA exposure induced both p53 dependent and independent apoptosis and morphological alterations in red blood cells but less sensitive to UVA than Wild type in medaka fish.

Condon Lau - One of the best experts on this subject based on the ideXlab platform.

  • single blood cell raman spectroscopy reveals elevated haemoglobin content in poikilocytosis
    Society of Photo-Optical Instrumentation Engineers (SPIE) Conference Series, 2019
    Co-Authors: Suet Man Tsui, Condon Lau
    Abstract:

    In this study, confocal Raman spectroscopy revealed biochemical differences between single normal red blood cells and poikilocytes. The intensities of 5 Raman bands associated with oxygenated RBCs are larger in Acanthocytes than normal and normal-looking RBCs. Overall, Acanthocytes carry more haemoglobin and this is corroborated by CBC and ICP-MS.

  • single blood cell raman spectroscopy reveals elevated haemoglobin content in poikilocytosis
    Imaging Manipulation and Analysis of Biomolecules Cells and Tissues XVII 2019, 2019
    Co-Authors: Suet Man Tsui, Rafay Ahmed, Condon Lau
    Abstract:

    Abnormally shaped red blood cells (poikilocytes) can cause serious health problems such as anemia and increase the risk of death. At present, the biochemical abnormalities in poikilocytes is not well understood, especially at the single cell level. In this study, confocal Raman spectroscopy revealed biochemical differences between single normal red blood cells (RBCs) and poikilocytes. Intragastric administration of nanoparticulate titanium dioxide (TiO2) was used to produce poikilocytes. Adult rats were administered by gavage 200mg/kg body weight TiO2 every other day for 20 days (low-dose, N=5) or 250mg/kg every day for 60 days (high-dose, N=5). Low and high-dose controls (N=5 each) were administered distilled water for equal durations. Raman spectroscopy was performed on individual RBCs of low-dose subjects using 514nm excitation and a confocal setup. Whole blood from high-dose subjects underwent a Complete Blood Count (CBC) and inductively coupled plasma mass spectrometry (ICP-MS). Acanthocytes and echinocytes, two types of poikilocytes, were observed from TiO2 subjects. RBCs were grouped into four types: normal RBCs from controls and normal-looking RBCs, Acanthocytes, and Echinocytes from TiO2 subjects. The intensities of Raman bands at 1637, 1585, 1559, 1372 and 1228cm-1 are larger in Acanthocytes than normal and normal-looking RBCs. The 1342cm-1 band is larger in normal RBCs, Acanthocytes and echinocytes than in normal-looking RBCs. Also, the 975cm-1 band is larger in Acanthocytes than normal-looking RBCs. These bands are associated with oxygenated RBCs. Overall, poikilocytes, especially Acanthocytes, carry more oxygen and haemoglobin and this is corroborated by CBC and ICPMS.

Alla Eldin Hamid Sayed - One of the best experts on this subject based on the ideXlab platform.

  • apoptosis and morphological alterations after uva irradiation in red blood cells of p53 deficient japanese medaka oryzias latipes
    Journal of Photochemistry and Photobiology B-biology, 2016
    Co-Authors: Alla Eldin Hamid Sayed, Tomomi Watanabeasaka, Shoji Oda, Hiroshi Mitani
    Abstract:

    Morphological alterations in red blood cells were described as hematological bioindicators of UVA exposure to investigate the sensitivity to UVA in wild type Japanese medaka (Oryzias latipes) and a p53 deficient mutant. The fewer abnormal red blood cells were observed in the p53 mutant fish under the control conditions. After exposure to different doses of UVA radiation (15min, 30min and 60min/day for 3days), cellular and nuclear alterations in red blood cells were analyzed in the UVA exposed fish compared with non-exposed controls and those alterations included Acanthocytes, cell membrane lysis, swollen cells, teardrop-like cell, hemolyzed cells and sickle cells. Those alterations were increased after the UVA exposure both in wild type and the p53 deficient fish. Moreover, apoptosis analyzed by acridine orange assay showed increased number of apoptosis in red blood cells at the higher UVA exposure dose. No micronuclei but nuclear abnormalities as eccentric nucleus, nuclear budding, deformed nucleus, and bilobed nucleus were observed in each group. These results suggested that UVA exposure induced both p53 dependent and independent apoptosis and morphological alterations in red blood cells but less sensitive to UVA than Wild type in medaka fish.