title: 5-Lipoxygenase DNA methylation and mRNA content in the brain and heart of young and old mice.
abstract: The expression of 5-lipoxygenase (5-LOX) is affected by aging and regulated by epigenetic mechanisms including DNA methylation. We used methylation-sensitive restriction endonucleases (AciI, BstUI, HpaII, and HinP1I) to assess 5-LOX DNA methylation in brain and heart tissue samples from young (2 months) and old (22 months) mice. We also measured mRNA content for 5-LOX and the DNA methyltransferases DNMT1 and DNMT3a. In young mice, the 5-LOX mRNA content was significantly greater in the heart compared to the brain; 5-LOX DNA methylation was lower, except in the AciI assay in which it was higher in the heart. Aging decreased 5-LOX mRNA content in the heart and increased it in the brain. Aging also increased 5-LOX DNA methylation and this effect was site- (i.e., enzyme) and tissue-specific. Generally, DNMT1 and DNMT3a mRNA content was lower in the brain regions compared to the heart; the only effect of aging was observed in the mRNA content of DNMT3a, which was decreased in the heart of old mice. These results indicate a complex tissue-specific and aging-dependent interplay between the DNA methylation system and 5-LOX mRNA content. Interpretation of this data must take into account that the tissue samples contained a mixture of various cell types.
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dzitoyeva
authors.forename: Marta
authors.initials: M
authors.lastname: Imbesi
authors.forename: Louisa W
authors.initials: LW
authors.lastname: Ng
authors.forename: Hari
authors.initials: H
authors.lastname: Manev
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001921:Brain / Q000201:enzymology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015289:Leukotrienes / Q000096:biosynthesis; D044045:Lipoxins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D015183:Restriction Mapping / Q000379:methods
chemical_list: C000715535:Dnmt3a protein, mouse; D015289:Leukotrienes; D044045:Lipoxins; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619381:Dnmt1 protein, mouse