| Full text | |
| Author(s): |
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]
Total Authors: 7
|
| Affiliation: | [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
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | GLYCOCONJUGATE JOURNAL; v. 38, n. 1 JAN 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 15/03964-6 - Glycosaminoglycans and proteoglycans: interplay between structure and function |
| Grantee: | Helena Bonciani Nader |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 11/00526-7 - Study of the role of Rho GTPases family members in the control of neuroblast migration |
| Grantee: | Layla Testa Galindo |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 17/18765-4 - Role of NOX-produced ROS in the activation of SHH signaling pathway during cerebellar development |
| Grantee: | Marimélia Aparecida Porcionatto |
| Support Opportunities: | Regular Research Grants |