Ultra low molecular weight heparin attenuates glutamate-induced neurotoxicity by reducing intracellular calcium release
- VernacularTitle:超低分子量肝素抑制神经细胞内钙释放保护谷氨酸损伤原代培养大鼠神经元
- Author:
Tiangui YU
;
Weiwei WANG
;
Qingzhu ZHANG
;
Shengli JI
- Publication Type:Journal Article
- Keywords:
ultra low molecular weight heparin;
glutamate;
calcium overload;
intracellular calcium release;
neuroprotection;
neurotoxicity
- From:
Chinese Pharmacological Bulletin
2003;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of ultra low molecular weight heparin(ULMWH)to protect primarily cultured rat cortical neurons from the deleterious effects of the neurotoxicant glutamate (Glu)and explore the related mechanism.Methods Cortical neurons of fetal rats were cultured carefully in vitro and treated with 100 ?mol?L-1 Glu so that the protective effects of ULMWH were observed thoroughly. And then the viability of cortical neurons, morphological change together with the number of apoptotic neurons,and the concentration of intracellular free Ca2+([Ca2+]i)were measured by MTT assay, Hoechst33258 staining and Fura-2/AM double wavelength fluoremetry, respectively.Results Brief exposure of cultures to 100 ?mol?L-1Glu led to extensive neuronal death and rapid increase of [Ca2+]i.Pretreatment with ULMWH over the concentration range of 0.01~1 mg?L-1 significantly inhibited the Glu-induced neuronal cell death assessed by a MTT assay and the number of apoptotic nuclei, evidenced by Hoechst 33258 staining.Glu-induced elevation of[Ca2+]i was decreased by pretreatment with 1 mg?L-1 ULMWH, which was indicated by Fura-2/AM not only in assay medium containing Ca2+ but also in Ca2+-free assay medium.Conclusions Those results suggest that ULMWH protects the cultured neurons from Glu-induced neurotoxicity, which may be attributed to its alleviating intracellular free Ca2+ overload via suppressing intracellular Ca2+ release from internal stores induced by Glu.
