1996 Fiscal Year Final Research Report Summary
The role of arachidonic 12-lipoxygenase products in the pathogenesis of cerebral ischemia
| Project/Area Number |
07457315
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | TOTTORI UNIVERSITY |
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Principal Investigator |
WATANABE Takashi Tottori Univ.Faculty of Medicine Associate Professor, 医学部, 助教授 (00175100)
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| Co-Investigator(Kenkyū-buntansha) |
KAMITANI Hideki Tottori Univ.Faculty of Medicine Assistant, 医学部附属病院, 助手 (70194967)
KONDO Shinji Tottori Univ.Faculty of Medicine Assistant, 医学部附属病院, 助手 (60192069)
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| Project Period (FY) |
1995 – 1996
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| Keywords | cerebral ischemia / neuron / vascular endothelium / arachidonic acid / 12-lipoxygenase |
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| Research Abstract |
Uptake of arachidonic acid 12-lipoxygenase products into canine brain tissue including cerebral artery and cultured human umblical cord vein endothelium was investigated. Radio-labelled 12-hydroperoxy-eicosatetraenoic acid (12-HPETE) and 12-hydroxyeicosatetraenoic acid (12-HETE) were produced and purified by recombinant human platelet 12-lipoxygenase using ^<14>C-labelled arachidonic acid.
Radio-labelled 12-HPETE (0.5mg) was injected into canine cisterna magna and the whole brain was removed sequentially to be applied to autoradiography. 12-HPETE was incorporated to brain tissue maximally 3 hours after the injection and its content decreased gradually but radio activity was still present even 3 weeks after the injection. It was also interesting that 12-HPETE disappeared from cerebrospinal fluid within 6 hors after the injection.
Radio-labelled 12-HPETE,12-HETE,and arachidonic acid were added to cultured vascular endothelium at concentration of 10^<-8>-10^<-5>M.Taken-up12-HPETE into cultured entothelium was maximum 12 hours after its application and was decreased gradually. Amount of incorporated 12-HPETE was as same as that of 12-HETE and nearly one third of arachidonic acid. Incorporation of 12-HPETE,12-HETE,and arachidonic acid were increased concentration-dependently. 12-HPETE and 12-HETE did not cause any cell damage morphologically.
Rather persistent incorporation of these lipidperoxides into cells and tissues may play roles of pathogenesis of cerebral arterial vasospasm, atherosclerosis, and brain damage.
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