The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA.
Neural Plast. 2009;2009:209596. doi: 10.1155/2009/209596. Epub 2009 Dec 13.
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.
5-脂氧合酶（5-LOX）的表达受衰老的影响，并受包括 DNA 甲基化在内的表观遗传机制调控。我们使用甲基化敏感的限制性内切酶（AciI、BstUI、HpaII 和 HinP1I）来评估年轻（2 个月）和年老（22 个月）小鼠的大脑和心脏组织样本中的 5-LOX DNA 甲基化。我们还测量了 5-LOX、DNA 甲基转移酶 DNMT1 和 DNMT3a 的 mRNA 含量。在年轻小鼠中，5-LOX mRNA 含量在心组织中明显高于脑组织；5-LOX DNA 甲基化程度较低，除了在 AciI 测定中，心组织中 5-LOX DNA 甲基化程度较高。衰老使心脏中的 5-LOX mRNA 含量降低，使大脑中的 5-LOX mRNA 含量增加。衰老还增加了 5-LOX DNA 甲基化，这种效应具有位点（即酶）和组织特异性。一般来说，脑区的 DNMT1 和 DNMT3a mRNA 含量低于心脏；只有衰老对心脏中 DNMT3a 的 mRNA 含量有影响，使老年小鼠心脏中的 DNMT3a mRNA 含量降低。这些结果表明，DNA 甲基化系统和 5-LOX mRNA 含量之间存在复杂的组织特异性和衰老依赖性相互作用。解释这些数据必须考虑到组织样本中包含各种细胞类型的混合物。
