Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1
10.11665/j.issn.1000-5048.20160217
- VernacularTitle:N-酰基葡糖胺衍生物对GABA转运体功能的影响
- Author:
Jing HU
1
;
Hua FAN
;
Jian YIN
Author Information
1. 江南大学无锡医学院
- Publication Type:Journal Article
- Keywords:
γ-aminobutyric acid(GABA);
N-glycosylation;
sialic acid;
N-acyl glucosamines;
central nervous system disease
- From:
Journal of China Pharmaceutical University
2016;47(2):228-234
- CountryChina
- Language:Chinese
-
Abstract:
In order to screen the inhibitors of GAT1 protein, the effects of synthetic N-acylglucosamines on the GABA uptake activity of GAT1 were examined in the HEK-293 cell model stably expressing GAT1 by performing GABA uptake assay. And since the N-linked oligosaccharides, especially their terminal sialic acid of GAT1 are necessary for the function of GAT1, their effects on the modification of N-glycans of GAT1 were also determined by the quantitative analysis of the sialic acid of GAT1. The results showed that 10 mmol /L 3-O-methyl-N-acetylglucosamine(3-O-Met-GlcNAc)reduced the GABA uptake activity of GAT1 to 53%(P< 0. 01)through inhibiting the sialylation of GAT1(66. 8%). And the GABA uptake activities were decreased to 54%, 63%, 63% and 67%(P< 0. 01), respectively, by the treatments of 10 mmol /L N-propionylglucosamine(GlcNProp), N-hexanoylglucosamine(GlcNHex), N-cycloproylgormylglucosamine(GlcNCyclo)and N-acetamidoacetylglucosamine(GlcNAc-acetamido)through inhibiting N-glycan trimming. These results indicate that the analogues of glucosamines have great potential in the development of inhibitors of GAT1 activity or sialic acid biosynthesis.
