Medhora M, Harder D
Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226, USA.
Int J Mol Med. 1998 Dec;2(6):661-9. doi: 10.3892/ijmm.2.6.661.
The list of functions attributed to astrocytes in the brain is ever increasing. These cells contain cytochrome P450 enzymes that have recently demonstrated a number of exciting roles besides detoxification. The P450 monooxygenases can covert the substrate arachidonic acid to epoxyeicosatrienoic acids (EETs), metabolites that mediate vasodilation, mitogenesis, platelet aggregation, Ca2+ signaling and steroidogenesis. Integration of other physiological pathways present in astrocytes with P450 mediated EET formation has generated a number of interesting hypotheses to yield deeper insight into the role of astrocytes in the brain. In order to test these hypotheses as well as to enhance the benefits of EETs in astrocytes, we have used viral-mediated gene transfer and overexpression of one cytochrome P450 monooxygenase, 2C11, to engineer astrocytes for gene manipulation and possible gene therapy. This review outlines evidence for the presence of EETs in astrocytes, the function of EETs and the progress made with viral vectors expressing epoxygenase for gene manipulation in astrocytes.
人们认为星形胶质细胞在大脑中的功能列表一直在增加。这些细胞含有细胞色素P450酶，最近除了解毒作用外，还显示出许多令人兴奋的作用。P450单加氧酶可以将底物花生四烯酸转化为环氧二十碳三烯酸（EETs），这些代谢产物介导血管舒张、有丝分裂、血小板聚集、Ca2+信号传导和类固醇生成。星形胶质细胞中存在的其他生理途径与P450介导的EET形成的整合产生了许多有趣的假设，以便更深入地了解星形胶质细胞在大脑中的作用。为了验证这些假设以及增强EETs在星形胶质细胞中的益处，我们使用病毒介导的基因转移和一种细胞色素P450单加氧酶2C11的过表达来改造星形胶质细胞以进行基因操作和可能的基因治疗。这篇综述概述了星形胶质细胞中存在EETs的证据、EETs的功能以及在星形胶质细胞中表达环氧酶用于基因操作的病毒载体所取得的进展。
