| Project/Area Number |
10671316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | SAITAMA MEDICAL SCHOOL |
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Principal Investigator |
MATSUI Toru SAITAMA MEDICAL SCHOOL, Associate Professor, 医学部, 助教授 (70199735)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Tamiki SAITAMA MEDICAL SCHOOL, Assistant, 医学部, 助手 (30275888)
MORIKAWA Eiharu SAITAMA MEDICAL SCHOOL, Lecturer, 医学部, 講師 (90251256)
MORIMOTO Tadashi SAITAMA MEDICAL SCHOOL, Lecturer, 医学部, 講師 (20230154)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Chronic vasospasm / protein kinase c / oxidized diacylglycerol / Subarachnoid hemorrhage / smooth muscle contraction / free radical / Skinned fiber / β-escin / β-エスチン / クモ膜下出血 / b-エスチン / マキンド ファイバー / 1.2.ジアシルグリセロール / 過酸化ジアシルグリセロール |
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| Research Abstract |
We have already reported the following experimental evidence suggesting that PKC (protein kinase C) activation participates in the occurrence of chronic vasospasm following subarachnoid hemorrhage. 1] The canine basilar artery (BA) possesses a PKC system which fully functions even in the Ca^<2+>-free medium, and that the narrowing or the augmented tonus of the BA exposed to 'two-hemorrhage' can be reversed by application of PKC inhibitors such as H-7 and staurosporine either in vivo or in vitro condition. 2] The content of 1,2-diacylglycerol, an intrinsic PKC activator, is significantly increased through the stimulated turnover of phosphatidylcholine and phosphatidylethanolamine in the spastic BA in comparison with that in the nonspastic BA.3] In spastic arteries at Days 4 and 7, the cytosolic PKC activity showed a decrease of 40-45% with no significant changes in membrane PKC activity as compared with nonspastic control arteries. The extent of 20 kDa myosin light chain phosphorylation
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was unchanged between the spastic and nonspastic BA.On Day 14, the cytosolic PKC activity of arteries returned toward the normal control level with the remission of vasospasm. Western blot analysis of the PKC isoforms revealed that the amounts of PKCα and PKCε but not PKCζ were down-regulated in spastic arteries, suggesting the activation of PKCα and PKCε in the course of chronic vasospasm. 4] The augmentation of active smooth muscle contraction, possibly induced by PKC activation, plays a role in the occurence of chronic vasospasm which is more important than the altered passive physical properties of the arterial wall (decreased dispensability of arterial wall). 5] In addition, it is revealed that oxidized diacylglycerol induces sustained contraction of normal and skinned BA.Under the pCa=5.5, an incubation of skinned basilar artery with palmitoyl-arachidonyl diacylglycerol-hydroperoxide (5xl0^<-5>M) shows a remarkable down-regulation of PKC a and e. As it is known that the down-regulation of the protein is the direct evidence to show its preceding activation, the oxidized-diacylglycerol induced contraction is thought to be mediated by an activation of PKC a orε. 6] Finally, PAG=OH and PLG-OH as an oxidized DAG were found in the brain tissue subjected to experimental subarachnoid hemorrhage. The above line of investigations render it likely that PKC activation, especially type e which is though to play a central role in the calciun-independent mechanism of smooth muscle contraction, participates in the occurrence of chronic vasospasm following subarachnoid hemorrhage Less
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