Navegando por Palavras-chave "Calcium cytoplasmic overload"

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    Efeito do dissacarídeo trissulfatado da heparina (DT) na morte neuronal desencadeada pela sobrecarga citoplasmática de cálcio
    (Universidade Federal de São Paulo (UNIFESP), 2018-06-28) Chiarantin, Gabrielly Maria Denadai [UNIFESP]; Porcionatto, Marimelia [UNIFESP]; http://lattes.cnpq.br/6155537170968904; http://lattes.cnpq.br/1633006298297954; Universidade Federal de São Paulo (UNIFESP)
    Neurons submitted to hypoxia undergo intense cytoplasmic Ca2+ overload. High concentrations of intracellular Ca2+ can trigger processes of cell death along the neural tissue, a pathological hallmark of Stroke. Ca2+ homeostasis in neurons involves the regulation of the intracellular concentration of Ca2+ ([Ca2+]i) by the Na+/Ca2+ exchanger (NCX), which plays an important role in the efflux of this ion. Previous data published by our group show that Trisulfated Disaccharide (TD), ΔU, 2S-GlcNS, 6S, the enzymatic degradation product of heparin, is able to accelerate Na+/Ca2+ exchange via NCX in hepatocytes and in smooth muscle cells of aorta. The objective of this work was to verify if TD is a neuroprotective agent able to prevent neuronal death by the reduction of [Ca2+]i induced by the cytoplasmic Ca2+ overload. The first part of the project was carried out in vitro, with the induction of neuronal death by cytoplasmic Ca2+ overload in murine neuroblastoma cell line (Neuro-2a), by different inducers of cytoplasmic elevation of Ca2+, such as: ATP (via purinergic receptor activation), Tapsgargin (via Ca-ATPase inhibition (SERCA) of the endoplasmic reticulum), Aspartate and Glutamate (via NMDAR activation) in the presence or absence of TD. The results showed that TD pretreatment is able to reduce cell death and increase the neuronal viability triggered by cytoplasmic Ca2+ overload. Cytoplasmic transient analysis of Ca2+ has shown that TD acts in a dose-dependent manner in reducing [Ca2+]i concentration, and this effect of TD is blocked by the NCX inhibitor, KBR7943. Considering these preliminary data, the second part of the project was carried out in a murine model submitted to cortical ischemia by photothrombosis, model of Stroke. The data indicate that pretreatment with TD in vivo is able to decrease the area of the ischemic lesion, an effect blocked by the NCX antagonist, as well as to decrease apoptotic death. Thus, we propose DT-NCX as a new therapeutic axis in the prevention of death triggered by cytoplasmic calcium overload.