Journal article
Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived
Journal of neurochemistry, Vol.57(3), pp.922-929
09/1991
DOI: 10.1111/j.1471-4159.1991.tb08239.x
Abstract
12‐Hydroxyeicosatetraenoic acid (12‐HETE) production from arachidonic acid by cerebral microvessels isolated from perfused adult murine brain was reduced by the lipoxygenase inhibitors baicalein, esculetin, gossypol, nordihydroguaiaretic acid, and quercetin. Except for quercetin and gossypol, the IC50 did not exceed 10 μM. Each inhibitor, except baicalein, also decreased microvessel prostaglandin production when present in concentrations above their IC50 value for 12‐HETE. In contrast, inhibitors of the cytochrome P450 monooxygenase system, clotrimazole. metyrapone, and proadifen (SKF‐525A), had little effect on microvessel 12‐HETE production. Chiral phase HPLC analysis revealed that only the (5) enantiomer of 12‐HETE was formed. The major microvessel metabolite of eicosapentaenoic acid co‐eluted with 12‐hydroxyeicosapentaenoic acid (12‐HEPE) on reverse‐phase HPLC and the (S) enantiomer of 12‐HEPE on chiral phase HPLC. Furthermore, like 12‐HETE. 12‐HEPE production was blocked by lipoxygenase inhibitors. These studies demonstrate that brain microvessels produce only the (5) enantiomeric 12‐hydroxy derivatives of both arachidonic acid and eicosapentaenoic acid by the action of a lipoxygenase that can be selectively inhibited by baicalein. Since arachidonic acid and eicosapentaenoic acid are available to cerebral blood vessels in certain pathological settings, these 12‐hydroxy acid lipoxygenase products may mediate some of the cere‐brovascular dysfunction that occurs following stroke, brain trauma, or seizures.
Details
- Title: Subtitle
- Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived
- Creators
- Steven A Moore - University of IowaMichael J Giordano - University of IowaHee‐Yong KimNorman Salem - National Institutes of HealthArthur A Spector - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of neurochemistry, Vol.57(3), pp.922-929
- Publisher
- Blackwell Publishing Ltd
- DOI
- 10.1111/j.1471-4159.1991.tb08239.x
- ISSN
- 0022-3042
- eISSN
- 1471-4159
- Number of pages
- 8
- Language
- English
- Date published
- 09/1991
- Academic Unit
- Biochemistry and Molecular Biology; Internal Medicine; Pathology
- Record Identifier
- 9984186572702771
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