1996 Fiscal Year Final Research Report Summary
Abnormal expression of phospholipases A_2 and human diseases
| Project/Area Number |
07307028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 総合 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Showa University |
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Principal Investigator |
KUDO Ichiro Showa University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30134612)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Masayoshi Fukuoka University, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (80131803)
ARAI Hiroyuki Tokyo University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40167987)
KOIKE Kaoru Nippon Medical School, Dept.of Emergency & Critical Care Medicine, Assistant, 付属千葉北総病院・救命救急部, 助手 (10267164)
HONDA Zen-ichiro Tokyo University, Faculty of Medical Sciences, Research Assistant, 物療内科, 助手 (70238814)
TAGAMI Seiichi Hokkaido University, Faculty of Medical Sciences, Research Assistant, 医学部, 助手 (80241305)
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| Project Period (FY) |
1995 – 1996
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| Keywords | phospholipases A_2 / nephritis / multi-organ dysfunction / diabetes / breast carcinoma / PAF-acetylhydrolase / immediate allergy |
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| Research Abstract |
We have examined the expression and function of phospholipase A_2 (PLA_2) isoforms that are implicated in arachidonate metabolism and their possible prticipation in human diseases.
1. Analysis of PLA_2 isoforms
(1) Cytosolic PLA_2 (cPLA_2) was expressed in various mamalian cells ubiquitously and consititutively. It was essential for the immediate phase of arachidonate methabolism that occurs within a few minutes after cell activation. In most cases, arachidonic acid released by cPLA_2 in the immediate phase was converted to prostanoids by constitutive cyclooxygenase COX-1.
(2) Secretory type II PLA_2 was induced in various types of cell in response to proinflammatory stimuli. This enzyme was functionally coupled with inducible COX-2 to provide delayd phase of prostanoid generation that lasts for several hours.
(3) Two novel secretory PLA_2 members, type IIC and V,were cloned from testis and heart, respectively. Recombinant expression of these enzymes was carried out. the expression and function of these PLA_2s in mammalian cells are currently under investigation.
2. Implication of PLA_2 isozymes in human diseases
(1) Multiple organ dysfunction : Gut ishchemia/reperfusion in the rat, used as a model system, caused lung injury via a mechanism which involved type II PLA_2.
(2) Rheumatoid arthritis : There was significant correlation between IL-6 and type II PLA_2 in the synovial fluid of patients with rheumatoid arthritis.
(3) Diabetes : Platelets from patients with diabetes contained higher level of cPLA_2 than normal littermates.
(4) Cancer : Several lung carcinomas were found to contain some unknown cPLA_2-inhibitory substances.
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