| Project/Area Number |
08457039
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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 |
General medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAMOTO Shozo The University of Tokushima, School of Medicine Department of Biochemistry Professor, 医学部, 教授 (50025607)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hiroshi The University of Tokushima, School of Medicine Department of Biochemistry Lectu, 医学部, 講師 (80253194)
林 陽子 徳島大学, 医学部, 助手 (60035441)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Archidonic acid / Cyclooxygenase / Lipoxygenase / Isozyme / Prostaglandin / Enzyme induction / Transcriptional regulation / Biomedulator |
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| Research Abstract |
There are two isozymes of 12-lipoxygenase distinguishable in terms of substrate specificity and primary structure. Two cycloowoygenase isozymes are known : the previously known enzyme (COX-1) and the recently found isozyme (COX-2). Their physiological and pathological functions are subjects of active invesigations. This research project is for the studies on the induction of the isozymes in pathophysiological conditions and the transcriptional regulation of the isozyme genes, and the following experimental results were obtained.
1) Transcriptional regulation of COX-1 gene : Addition of a phorbol ester induced COX-1 in human megakaryoblastic cells CMK along with their differentiation to megakaryocytes. We found the presence of prostaglandin D synthase in megakaryoblasts which is absent in platelets.
2) Transcriptional regulation of COX-2 gene : Induction of COX-2 by TNFalpha was demonstrated with murine osteoblastic cells MC3T3-E1, and involvement of NFkappaB and NF-IL6 were shown. COX-2 induction was also observed in rat pluerisy model.
3) Suicide inactivation of 12-lipoxygenase isozymes : Leukocyte 12-lipoxygenase shows a marked inactivation during its catalysis while platelet 12-lipoxygenase reaction proceeded almost linearly. The suicide inactivation of the leukocyte enzyme was attributed to its production of 15-hydroperoxy acid in addition to 12-hydroperoxy acid and to the coversion of the former minor product to a 14,15-epoxide.
4) Transcriptional regulation of 12-lipoxygenase gene : In collaboration with Taiwanese group 12-lipoxygenase induction of EGF in human epidermoid carcinoma cells A431 was demonstrated, and involvement of SP-1 was suggested in the transcription of the enzyme gene. Furthermore, diurnal change of 12-lipoxygenase mRNA was observed in rat pineal gland.
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