Morphological changes induced in erythrocyte by amyloid beta peptide and glucose depletion: A combined atomic force microscopy and biochemical study |
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Authors: | Cristiana Carelli-Alinovi Simone Dinarelli Beatrice Sampaolese Francesco Misiti Marco Girasole |
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Institution: | 1. Human, Social and Health Department, University of Cassino and Lazio Meridionale, V. S. Angelo, Loc. Folcara, 03043 Cassino, FR, Italy;2. Biochemistry and Clinical Biochemistry Institute, Catholic University, School of Medicine, L. go F. Vito n.1, 00168 Rome, Italy;3. Institute for the Structure of the Matter (ISM), National Research Council (CNR), via Fosso del Cavaliere 100, 00133 Rome, Italy;4. Institute of Chemistry of the Molecular Recognition (ICRM), National Research Council (CNR), L. go F. Vito n.1, 00168 Rome, Italy |
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Abstract: | Circulating red blood cells (RBCs) undergo aging, a fundamental physiological phenomenon that regulates their turnover. We show that treatment with beta amyloid peptide 1–42 (Aβ) accelerates the occurrence of morphological and biochemical aging markers in human RBCs and influences the cell metabolism leading to intracellular ATP depletion. The morphological pattern has been monitored using Atomic Force Microscopy (AFM) imaging and measuring the RBCs' plasma membrane roughness employed as a morphological parameter capable to provide information on the structure and integrity of the membrane-skeleton. Results evidence that Aβ boosts the development of crenatures and proto-spicules simultaneously to acceleration in the weakening of the cell-cytoskeleton contacts and to the induction of peculiar nanoscale features on the cell membrane. Incubation in the presence of glucose can remove all but the latter Aβ-induced effects.Biochemical data demonstrate that contemporaneously to morphological and structural alterations, Aβ and glucose depletion trigger a complex signaling pathway involving caspase 3, protein kinase C (PKC) and nitric oxide derived metabolites.As a whole, the collected data revealed that, the damaging path induced by Aβ in RBC provide a sequence of morphological and functional intermediates following one another along RBC life span, including: (i) an acceleration in the development of shape alteration typically observed along the RBC's aging; (ii) the development of characteristic membrane features on the plasma membrane and (iii) triggering a complex signaling pathway involving caspase 3, PKC and nitric oxide derived metabolites. |
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Keywords: | Amyloid beta peptide RBC Nitric oxide synthase PKC Caspase 3 Atomic force microscopy Membrane roughness |
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