Effects of 5-Aza-2'-deoxycytidine on expression of PP1γ in learning and memory.
BACKGROUND
Learning and memory is a complex process. Some reports have shown that protein kinases (PKs) and phosphatases (PPs) are important mediators in this process. And it is also well known that protein serine/threonine phosphatase 1 (PP1) and DNA methylation are critically involved in learning and memory.


METHODS
In the current study, the mice and cultured cells (NG108-15) were treated with vehicle or 5-Aza-2'-deoxycytidine (5-aza-cdR), a DNA methyltransferase (DNMT) inhibitor. The ability of learning and memory of mice was detected by Morris Water Maze, while the mRNA and protein expression levels of DNMTs and PP1γ in mice hippocampus were measured by real-time PCR and western-blot. To further clarify whether the 5-aza-cdR effects on learning and memory depend on cell proliferation/apoptosis or not, the effects of 5-aza-cdR on the cell proliferation, apoptosis, and PP1γ transcriptional activity were analyzed by using the xCelligence system, flow cytometer and Luciferase reporter assay, respectively.


RESULTS
The ability of learning and memory was increased while the expressions of DNMTs and PP1γ were decreased in the hippocampus of mice which were injected with 5-aza-cdR. In vitro experiments showed 10μM 5-aza-cdR inhibited cell proliferation, decreased PP1γ transcription without inducing apoptosis.


CONCLUSIONS
Our data demonstrate that the 5-aza-cdR restrains the expression of PP1γ which is related to learning and memory in the mice.
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Zhuxia
Z
Zhang
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Jie
J
Yang
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Xiaolei
X
Liu
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Xiaoe
X
Jia
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Shengdi
S
Xu
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China; Department of Oral and Maxillofacial Surgery, University of California San Francsico, San Francisco, USA.
Kerui
K
Gong
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China.
Shaochun
S
Yan
Department of Neurosurgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia, People's Republic of China. Electronic address: zhangchunyangbyyfy@163.com.
Chunyang
C
Zhang
Biomedicine Research Center and Basic Medical Department, Baotou Medical College, Inner Mongolia, People's Republic of China; Beijing key laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China. Electronic address: shao_guo_china@163.com.
Guo
G
Shao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D018782:Maze Learning / Q000187:drug effects*; D008813:Mice, Inbred ICR; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000077209:Decitabine; D015254:DNA Modification Methylases; C517103:Ppp1cc protein, mouse; D054645:Protein Phosphatase 1; D001374:Azacitidine
5-aza-cdR; Hippocampus; Learning and memory; PP1γ