Down-regulation of beta1,4GalT V at protein level contributes to arsenic trioxide-induced glioma cell apoptosis.
Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis with largely unknown mechanisms. Posttranslational processing of proteins by glycosylation could have multiple regulating roles in the process of apoptosis. Here, we found that the expression of beta1,6-linked GlcNAc-bearing N-glycans on cell surface protein was gradually decreased after induction of apoptosis by As2O3-treatment. And, As2O3 significantly decreased the protein expression level of beta1,4GalT V, which effectively galactosylates the beta1,6-GlcNAc branch of N-glycans and functions as a positive regulator in glioma development. Furthermore, interfering with the expression of beta1,4GalT V in human glioma cell markedly promoted As2O3-induced cell apoptosis and beta1,4GalT V overexpression significantly reduced As2O3-induced glioma cell apoptosis. Taken together, our results suggested that down-regulation of beta1,4GalT V expression plays an important role in As2O3-induced apoptosis, providing a new mechanism of As2O3-induced cell apoptosis and indicating that inhibitors of beta1,4GalT V may enhance the therapeutic efficiency of As2O3 for malignant glioma.
Wei
Yuanyan
Y
Key Laboratory of Glycoconjuates Research, Ministry of Public Health & Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
Liu
Dan
D
Ge
Yuqing
Y
Zhou
Fengbiao
F
Xu
Jiejie
J
Chen
Hong
H
Yun
Xiaojing
X
Gu
Jianxin
J
Jiang
Jianhai
J
D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000494:pharmacology; D015536:Down-Regulation; D005700:Galactosyltransferases / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020221:Optic Nerve Injuries; D010087:Oxides / Q000494:pharmacology*; D011134:Polysaccharides / Q000378:metabolism
D001152:Arsenicals; D016373:DNA, Antisense; D010087:Oxides; D011134:Polysaccharides; D005700:Galactosyltransferases; C493310:beta1,4-galactosyltransferase, human; D000077237:Arsenic Trioxide