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DNA hydroxymethylation mediated traumatic spinal injury by influencing cell death–related gene expression
Author(s) -
Sun Hao,
Miao Zhigang,
Wang Hua,
Tao Yuping,
Yang Jiandong,
Cai Jun,
Wang Jingcheng,
Wang Yongxiang
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27200
Subject(s) - 5 hydroxymethylcytosine , epigenetics , dna demethylation , programmed cell death , messenger rna , spinal cord , spinal cord injury , gene , gene expression , biology , cell , dna methylation , microbiology and biotechnology , medicine , apoptosis , genetics , neuroscience
Spinal cord injury (SCI) is a serious neurological disease, often leading to segmental injury following severe limb dysfunction. Recent studies showed that epigenetic regulation is involved in the pathogenesis of SCI. In this study, we examined the change in 5‐hydroxymethylcytosine (5hmC), a mechanism of demethylation, and its role in SCI in rats. We found that global 5hmC modification significantly increased in traumatic spinal cord tissues. Ten‐eleven translocation (Tet) enzymes are the limiting‐rate enzyme to catalyze the conversion of 5‐methylcytosine to 5hmC. In our study, the data indicated that Tet2, but not Tet1 and Tet3, significantly increased in traumatic spinal cord tissues. Further, we treated rats with SC‐1, a Tet2 expression inhibitor. SC‐1 increased necrotic volume after SCI. To further demonstrate that the damage caused by SC‐1 was related to DNA 5hmC, we examined the messenger RNA (mRNA) expression of many genes that related to cell death and cell survival. Our data showed that the 5hmC levels were related to the mRNA levels of these genes. In conclusion, targeting Tet2 to cause change in 5hmC levels in cell death–related genes may be new therapeutic strategy for the treatment of SCI.