PMID- 23619570
OWN - NLM
STAT- MEDLINE
DCOM- 20131028
LR  - 20171116
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 45
IP  - 5
DP  - 2013 May
TI  - Hyperhomocysteinemia induces cardiac injury by up-regulation of p53-dependent 
      Noxa and Bax expression through the p53 DNA methylation in ApoE(-/-) mice.
PG  - 391-400
LID - 10.1093/abbs/gmt030 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease and has a 
      strong correlation with heart failure. However, the effects of HHcy on cardiac 
      tissue remain less well understood. To elucidate the role of p53-dependent 
      apoptosis in HHcy-induced cardiac injury, we fed ApoE(-/-) mice with high 
      methionine diet to establish HHcy model. Serum Hcy, cardiac enzymes, and lipids 
      were measured. The protein levels of Noxa, DNMT1, caspases-3/9, and p53 were 
      determined by enzyme-linked immunosorbent assay. Bcl-2 and Bax proteins were 
      detected by immunohistochemistry staining. S-adenosyl methionine and S-adenosyl 
      homocysteine concentrations were determined by high-performance liquid 
      chromatography. The mRNA levels of p53 and DNMT1 were analyzed by real-time 
      polymerase chain reaction (PCR) and the methylation levels of p53 were analyzed 
      by nested methylation-specific-PCR. Our data showed that the concentrations of 
      serum Hcy and lipids were increased in Meth group compared with the N-control 
      group, which indicated that the model was established successfully. The 
      expression levels of p53 and Noxa were increased in Meth group, while the 
      methylation status of p53 was hypomethylation. The activities of caspase-3/9 were 
      increased in Meth group compared with the N-control group. In addition, 
      immunohistochemistry staining showed that the expression of Bax was significantly 
      increased in Meth and Meth-F group compared with the N-control group. In summary, 
      HHcy induces cardiac injury by up-regulation of p53-dependent pro-apoptotic 
      related genes Noxa and Bax, while p53 DNA hypomethylation is a key molecular 
      mechanism in pathological process induced by HHcy.
FAU - Ma, Shengchao
AU  - Ma S
AD  - Department of Laboratory Medical, Ningxia Medical University, Yinchuan 750004, 
      China.
FAU - Zhang, Huiping
AU  - Zhang H
FAU - Sun, Weiwei
AU  - Sun W
FAU - Gong, Huihui
AU  - Gong H
FAU - Wang, Yanhua
AU  - Wang Y
FAU - Ma, Changjian
AU  - Ma C
FAU - Wang, Ju
AU  - Wang J
FAU - Cao, Chengjian
AU  - Cao C
FAU - Yang, Xiaoling
AU  - Yang X
FAU - Tian, Jue
AU  - Tian J
FAU - Jiang, Yideng
AU  - Jiang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (Apolipoproteins E)
RN  - 0 (Pmaip1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (Dnmt1 protein, mouse)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*deficiency
MH  - Cardiomyopathies/*etiology/physiopathology
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/biosynthesis
MH  - DNA Methylation
MH  - Hyperhomocysteinemia/*physiopathology
MH  - Male
MH  - Mice
MH  - Proto-Oncogene Proteins c-bcl-2/*biosynthesis
MH  - Tumor Suppressor Protein p53/*genetics
MH  - Up-Regulation
MH  - bcl-2-Associated X Protein/*biosynthesis
EDAT- 2013/04/27 06:00
MHDA- 2013/10/29 06:00
CRDT- 2013/04/27 06:00
PHST- 2013/04/27 06:00 [entrez]
PHST- 2013/04/27 06:00 [pubmed]
PHST- 2013/10/29 06:00 [medline]
AID - gmt030 [pii]
AID - 10.1093/abbs/gmt030 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2013 May;45(5):391-400. doi: 
      10.1093/abbs/gmt030.