Temporal changes of cytochrome P450 (Cyp) and eicosanoid-related gene expression in the rat brain after traumatic brain injury.
Temporal changes of cytochrome P450 (Cyp) and eicosanoid-related gene expression in the rat brain after traumatic brain injury.
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DOI：
10.1186/1471-2164-14-303
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发表时间：
2013-05-04
期刊：
影响因子：
4.4
通讯作者：
Strauss KI
中科院分区：
文献类型：
--
作者：
Birnie M;Morrison R;Camara R;Strauss KI
创伤性脑损伤（TBI）诱导细胞膜花生四烯酸（ArA）释放。ArA代谢物形成一类超过50种生物活性类花生酸，可以诱导适应性和/或适应不良的脑反应。ArA到类花生酸的动态代谢，以及它们如何影响受伤的大脑，由于其不同的活动，痕量水平和短半衰期而知之甚少。损伤后大脑中产生的类花生酸依赖于任何给定时间局部存在的酶。类二十烷酸由含血红素的酶合成，包括环氧合酶、脂氧合酶和花生四烯酸单加氧酶。后者包括代谢脂肪酸、类固醇以及内源性和外源性毒物的细胞色素P450“Cyp”基因家族的子集。然而，对于这些基因中的许多基因，在大脑中既没有研究基线神经解剖学也没有研究损伤相关的时间表达。在大鼠顶叶皮层TBI模型中，观察了伤后6 h、24 h、3 d和7 d顶叶皮层和海马中Cyp和类花生酸相关的mRNA水平的动态变化。定量实时聚合酶链反应与低密度阵列被用来分析62大鼠Cyps，其中37代谢ArA或其他不饱和脂肪酸; 16类花生酸相关酶代谢ArA或其代谢产物; 8类花生酸受体; 5其他炎症和恢复相关基因，加上2小鼠Cyps作为阴性对照和3个高表达的“管家”基因。16种花生四烯酸单加氧酶、17种类花生酸相关基因和12种其他Cyps在脑损伤后受到调节（p < 0.05，Tukey HSD）。海马和顶叶皮层中观察到离散的组织水平和不同的损伤后基因表达的时间模式。结果表明TBI后ArA和其他脂质代谢的复杂调节。由于脑损伤诱导的Cyp基因诱导的时间性质，需要在TBI后的给定时间操作每个基因（或其产物）以评估其对继发性损伤和/或恢复的贡献。此外，更好地了解大脑区域定位和细胞类型特异性表达可能是必要的，以推断这些类花生酸相关基因在健康和受伤的大脑中的作用。
Traumatic brain injury (TBI) induces arachidonic acid (ArA) release from cell membranes. ArA metabolites form a class of over 50 bioactive eicosanoids that can induce both adaptive and/or maladaptive brain responses. The dynamic metabolism of ArA to eicosanoids, and how they affect the injured brain, is poorly understood due to their diverse activities, trace levels, and short half-lives. The eicosanoids produced in the brain postinjury depend upon the enzymes present locally at any given time. Eicosanoids are synthesized by heme-containing enzymes, including cyclooxygenases, lipoxygenases, and arachidonate monoxygenases. The latter comprise a subset of the cytochrome P450 “Cyp” gene family that metabolize fatty acids, steroids, as well as endogenous and exogenous toxicants. However, for many of these genes neither baseline neuroanatomical nor injury-related temporal expression have been studied in the brain. In a rat model of parietal cortex TBI, Cyp and eicosanoid-related mRNA levels were determined at 6 h, 24 h, 3d, and 7d postinjury in parietal cortex and hippocampus, where dynamic changes in eicosanoids have been observed. Quantitative real-time polymerase chain reaction with low density arrays were used to assay 62 rat Cyps, 37 of which metabolize ArA or other unsaturated fatty acids; 16 eicosanoid-related enzymes that metabolize ArA or its metabolites; 8 eicosanoid receptors; 5 other inflammatory- and recovery-related genes, plus 2 mouse Cyps as negative controls and 3 highly expressed “housekeeping” genes. Sixteen arachidonate monoxygenases, 17 eicosanoid-related genes, and 12 other Cyps were regulated in the brain postinjury (p < 0.05, Tukey HSD). Discrete tissue levels and distinct postinjury temporal patterns of gene expression were observed in hippocampus and parietal cortex. The results suggest complex regulation of ArA and other lipid metabolism after TBI. Due to the temporal nature of brain injury-induced Cyp gene induction, manipulation of each gene (or its products) at a given time after TBI will be required to assess their contributions to secondary injury and/or recovery. Moreover, a better understanding of brain region localization and cell type-specific expression may be necessary to deduce the role of these eicosanoid-related genes in the healthy and injured brain.
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DOI：
10.1016/s0006-291x(02)00918-x
发表时间：
2002-08-23
影响因子：
3.1
作者：
Bylund, J;Zhang, CY;Harder, DR
通讯作者：
Harder, DR
影响因子：
4.2
作者：
Dash, PK;Mach, SA;Moore, AN
通讯作者：
Moore, AN
影响因子：
56.9
作者：
Bowles, J;Knight, D;Koopman, P
通讯作者：
Koopman, P
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
影响因子：
4.7
作者：
Abdu E;Bruun DA;Yang D;Yang J;Inceoglu B;Hammock BD;Alkayed NJ;Lein PJ
通讯作者：
Lein PJ