5-Lipoxygenase DNA methylation and mRNA content in the brain and heart of young and old mice

Neural Plast. 2009;2009:209596. doi: 10.1155/2009/209596. Epub 2009 Dec 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Arachidonate 5-Lipoxygenase / genetics*
  • Brain / enzymology*
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation / genetics*
  • Down-Regulation / genetics
  • Epigenesis, Genetic / physiology
  • Gene Silencing / physiology
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Leukotrienes / biosynthesis
  • Lipoxins / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / enzymology*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • Restriction Mapping / methods

Substances

  • Leukotrienes
  • Lipoxins
  • RNA, Messenger
  • Arachidonate 5-Lipoxygenase
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A
  • Dnmt1 protein, mouse