Extracellular Spermine Activates DNA Methyltransferase 3A and 3B

International Journal of Molecular Sciences

卷:20

Toshiki Rikiyama¹  Kuniyasu Soda²  Taro Fukui³  Koichi Takao⁴ 

[1] Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan;

[2] Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, Saitama-city, Saitama 330-8503, Japan;

[3] Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama-city, Saitama 330-8503, Japan;

[4] Laboratory of Cellular Physiology, Department of Clinical Dietetics &

关键词: gene methylation;    methyltransferase;    DNA methyltransferase (DNMT);    polyamine;    spermine;    ornithine decarboxylase (ODC);    D,L-alpha-difluoromethylornithine (DFMO);    adenosylmethionine;   

DOI  :  10.3390/ijms20051254

来源: DOAJ

【 摘 要 】

We first demonstrated that long-term increased polyamine (spermine, spermidine, putrescine) intake elevated blood spermine levels in mice and humans, and lifelong consumption of polyamine-rich chow inhibited aging-associated increase in aberrant DNA methylation, inhibited aging-associated pathological changes, and extend lifespan of mouse. Because gene methylation status is closely associated with aging-associated conditions and polyamine metabolism is closely associated with regulation of gene methylation, we investigated the effects of extracellular spermine supplementation on substrate concentrations and enzyme activities involved in gene methylation. Jurkat cells and human mammary epithelial cells were cultured with spermine and/or D,L-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. Spermine supplementation inhibited enzymatic activities of adenosylmethionine decarboxylase in both cells. The ratio of decarboxylated S-adenosylmethionine to S-adenosyl-L-methionine increased by DFMO and decreased by spermine. In Jurkat cells cultured with DFMO, the protein levels of DNA methyltransferases (DNMTs) 1, 3A and 3B were not changed, however the activity of the three enzymes markedly decreased. The protein levels of these enzymes were not changed by addition of spermine, DNMT 3A and especially 3B were activated. We show that changes in polyamine metabolism dramatically affect substrate concentrations and activities of enzymes involved in gene methylation.

【 授权许可】

Unknown