Neuroprotective effect of heparin Trisulfated disaccharide on ischemic stroke

Autor(es)

Chiarantin, Gabrielly M. D. ^{[1, 2]} ; Delgado-Garcia, Lina M. ^{[1, 2]} ; Zamproni, Laura N. ^{[1, 2]} ; Lima, Marcelo A. ^{[1, 3]} ; Nader, Helena B. ^[1] ; Tersariol, Ivarne L. S. ^[1] ; Porcionatto, Marimelia ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Lab Mol Neurobiol, Sao Paulo, SP - Brazil

^[3] Keele Univ, Sch Life Sci, Mol & Struct Biosci, Newcastle Under Lyme ST5 5BG, Staffs - England

• Tipo de documento: Artigo Científico
• Fonte: GLYCOCONJUGATE JOURNAL; v. 38, n. 1 JAN 2021.
• Citações Web of Science: 0

Resumo

Cells undergoing hypoxia experience intense cytoplasmic calcium (Ca2+) overload. High concentrations of intracellular calcium ({[}Ca2+](i)) can trigger cell death in the neural tissue, a hallmark of stroke. Neural Ca2+ homeostasis involves regulation by the Na+/Ca2+ exchanger (NCX). Previous data published by our group showed that a product of the enzymatic depolymerization of heparin by heparinase, the unsaturated trisulfated disaccharide (TD; Delta U, 2S-GlcNS, 6S), can accelerate Na+/Ca2+ exchange via NCX, in hepatocytes and aorta vascular smooth muscle cells. Thus, the objective of this work was to verify whether TD could act as a neuroprotective agent able to prevent neuronal cell death by reducing {[}Ca2+](i). Pretreatment of N2a cells with TD reduced {[}Ca-i(2+]) rise induced by thapsigargin and increased cell viability under {[}Ca-I(2+]) overload conditions and in hypoxia. Using a murine model of stroke, we observed that pretreatment with TD decreased cerebral infarct volume and cell death. However, when mice received KB-R7943, an NCX blocker, the neuroprotective effect of TD was abolished, strongly suggesting that this neuroprotection requires a functional NCX to happen. Thus, we propose TD-NCX as a new therapeutic axis for the prevention of neuronal death induced by {[}Ca2+](i) overload. (AU)

• Processo FAPESP: 15/03964-6 - Glicosaminoglicanos e proteoglicanos: relação estrutura e função
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/00526-7 - Estudo do papel dos membros da família das Rho GTPases no controle da migração de neuroblastos
• Beneficiário: Layla Testa Galindo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/18765-4 - Papel de ROS produzido por NOX na ativação da via de SHH durante o desenvolvimento do cerebelo
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular