Neuroprotective effect of heparin Trisulfated disaccharide on ischemic stroke.

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Contributed Indexing: Keywords: Calcium overload; Hypoxia; Neuroprotection; Stroke; Trisulfated disaccharide
Substance Nomenclature: 0 (2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate)
0 (Disaccharides)
0 (Neuroprotective Agents)
0 (heparin disaccharide)
67526-95-8 (Thapsigargin)
9005-49-6 (Heparin)
GYV9AM2QAG (Thiourea)
SY7Q814VUP (Calcium)
Entry Date(s): Date Created: 20210107 Date Completed: 20220128 Latest Revision: 20240226
Update Code: 20240226
DOI: 10.1007/s10719-020-09966-4
PMID: 33411076
Autor: Chiarantin GMD; Laboratory of Molecular Neurobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Delgado-Garcia LM; Laboratory of Molecular Neurobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Zamproni LN; Laboratory of Molecular Neurobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Lima MA; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil.; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, Staffordshire, ST5 5BG, UK., Nader HB; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil., Tersariol ILS; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil. ivarne.tersariol@gmail.com., Porcionatto M; Laboratory of Molecular Neurobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil. marimelia.porcionatto@unifesp.br.; Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil. marimelia.porcionatto@unifesp.br.
Jazyk: angličtina
Zdroj: Glycoconjugate journal [Glycoconj J] 2021 Feb; Vol. 38 (1), pp. 35-43. Date of Electronic Publication: 2021 Jan 07.
DOI: 10.1007/s10719-020-09966-4
Abstrakt: Cells undergoing hypoxia experience intense cytoplasmic calcium (Ca 2+ ) overload. High concentrations of intracellular calcium ([Ca 2+ ] i ) can trigger cell death in the neural tissue, a hallmark of stroke. Neural Ca 2+ homeostasis involves regulation by the Na + /Ca 2+ 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; ΔU, 2S-GlcNS, 6S), can accelerate Na + /Ca 2+ 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 [Ca 2+ ] i . Pretreatment of N2a cells with TD reduced [Ca 2+] i rise induced by thapsigargin and increased cell viability under [Ca 2+] I 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 [Ca 2+ ] i overload.
Databáze: MEDLINE
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