| The lipoxygenase pathway of Tupaia belangeri representing Scandentia. Genomic multiplicity and functional characterization of the ALOX15 orthologs in the tree shrew | |
Schaefer, Marjann; Fan, Yu; Gu, Tianle; Heydeck, Dagmar; Stehling, Sabine; Ivanov, Igor; Yao, Yong-Gang ; Kuhn, Hartmut
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| 2020 | |
| 发表期刊 | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
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| ISSN | 1388-1981 |
| 卷号 | 1865期号:2 |
| 摘要 | The tree shrew (Tupaia belangeri) is a rat-sized mammal, which is more closely related to humans than mice and rats. However, the use of tree shrew to explore the patho-mechanisms of human inflammatory disorders has been limited since nothing is known about eicosanoid metabolism in this mammalian species. Eicosanoids are important lipid mediators exhibiting pro- and anti-inflammatory activities, which are biosynthesized via lipoxygenase and cyclooxygenase pathways. When we searched the tree shrew genome for the presence of cyclooxygenase and lipoxygenase isoforms we found copies of functional COX1, COX2 and LOX genes. Interestingly, we identified four copies of ALOX15 genes, which encode for four structurally distinct ALOX15 orthologs (tupALOX15a-d). To explore the catalytic properties of these enzymes we expressed tupALOX15a and tupALOX15c as catalytically active proteins and characterized their enzymatic properties. As predicted by the Evolutionary Hypothesis of ALOX15 specificity we found that the two enzymes converted arachidonic acid predominantly to 12S-HETE and they also exhibited membrane oxygenase activities. However, their reaction kinetic properties (K-M for arachidonic acid and oxygen, T- and pH-dependence) and their substrate specificities were remarkably different. In contrast to mice and humans, tree shrew ALOX15 isoforms are highly expressed in the brain suggesting a role of these enzymes in cerebral function. The genomic multiplicity and the tissue expression patterns of tree shrew ALOX15 isoforms need to be considered when the results of in vivo inflammation studies obtained in this animal are translated into the human situation. |
| 收录类别 | sci |
| 语种 | 英语 |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/12757 |
| 专题 | 科研部门_疾病机理遗传学和进化医学学科组（姚永刚） |
| 推荐引用方式 GB/T 7714 | Schaefer, Marjann,Fan, Yu,Gu, Tianle,et al. The lipoxygenase pathway of Tupaia belangeri representing Scandentia. Genomic multiplicity and functional characterization of the ALOX15 orthologs in the tree shrew[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,2020,1865(2). |
| APA | Schaefer, Marjann.,Fan, Yu.,Gu, Tianle.,Heydeck, Dagmar.,Stehling, Sabine.,...&Kuhn, Hartmut.(2020).The lipoxygenase pathway of Tupaia belangeri representing Scandentia. Genomic multiplicity and functional characterization of the ALOX15 orthologs in the tree shrew.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,1865(2). |
| MLA | Schaefer, Marjann,et al."The lipoxygenase pathway of Tupaia belangeri representing Scandentia. Genomic multiplicity and functional characterization of the ALOX15 orthologs in the tree shrew".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS 1865.2(2020). |
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| 2021110316.pdf（1843KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 请求全文 | |
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