The influence of ADAR1's regulation on lymphocyte cell function during rejection.
The RNA editing adenosine deaminase gene (ADAR1) expression is wide-spread in lymphocytes. We explore the mechanism of ADAR1 regulation on the function of T primary lymphocytes when rejection occurs by knock-down the expression of ADAR1 in mouse T primary lymphocytes in mixed lymphocyte cultures. The changes of cell proliferation, the expression of ADAR1 and the cell cycle related genes cyclin D1 and A1, cell cycle and apoptosis analysis and mouse gene expression profiles was evaluated. We found that treatment with ADAR1-specific siRNA inhibited allogenic antigen stimulated T cell proliferation, arrested T cell cycle at G(0)/G(1) phases and promoted T cell apoptosis, which was associated with down-regulation of some related key genes transcription. These findings suggest that ADAR1 is essential for the maintenance of function of T lymphocytes during acute rejection. The mechanism underlying ADAR1's action might include editing of a currently unknown substrate and interacting with other proteins.
Cai
Lei
L
Department of Hepato-Biliary Surgery, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China.
Li
Yan
Y
Liu
Feng
F
Zhang
Wei
W
Huo
Binliang
B
Zheng
Wei
W
Ding
Rui
R
Guo
Jiyuan
J
Zhao
Qingchuan
Q
Dou
Kefeng
K
D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D056750:Cyclin A1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D006084:Graft Rejection / Q000276:immunology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
D056750:Cyclin A1; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019938:Cyclin D1; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase