Functional role of epoxyeicosatrienoic acids and their production in astrocytes: approaches for gene transfer and therapy (review).
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.
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Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee 53226, USA.
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D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D000256:Adenoviridae; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D010105:Oxygenases / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D014664:Vasodilation
D013256:Steroids; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid