Studies on the tissue damage induced by activation of calpains under infarct/ischemia
| Project/Area Number |
07670177
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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 |
Pathological medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
SASAKI Makoto Nagoya City University Medical School, Professor, 医学部, 教授 (10080003)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Toyohiro Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (20106230)
HAYAKAWA Tomihiro Nagoya City University Medical School, Research Associate, 医学部, 助手 (50172995)
KUNIMATSU Mitoshi Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (70145746)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Calpain / Ischemia / Reperfusion / Calpain inhibitor / Miocardial infarction / NF-kappaB / Anti-calpain antibody / Neuronal cell death / 虚血再灌流 / μ-カルパイン前駆体 / 脳神経細胞死 / 神経芽細胞腫 / 心筋虚血再灌流 / NFχB |
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| Research Abstract |
The role of calpains in tissue damage and cell death under the conditions of infarction/ischemia was investigated. The initial study was carried out with rat heart, but later brains were employed as a target organ, because typical change was evidenced before and after ischemia.
1.Through ischemia/reperfusion of rat hearts, potential caseinolytic activity of calpains decreased to less than half in total, but the decrease was protected by the addition of calpain inhibitor I in the media before perfusion under ischemic conditions was carried out.
2.Various organ tissues were immunostained using antibodies against several antigenic determinants of mu- and m-calpains. The results showed that nuclei of neurons in both periferal and central nervous systems were densely stained and the staining mostly disappeared after ischemia/reperfusion. This change concided well with the degenerated areas elucidated by argyrophil III silver staining.
3.Densely stained nuclei were also observed with the cultured cells of neuroblasma cell lines and primary cultured neurons from rat brains. Neuronal cell death evaluated by the trypan blue exclusion test paralleled the disappearance of the staining. The cell death was time-dependent and it was efficiently prevented by the addition of calpain inhibitor I.
These results suggested that calpains may play a crucial role in the tissue damage induced by myocardial infarction and that exceptionally high sensitivity of brains to ischemic conditions may have a close relationship with the concentrated existence of pro mu-calpain in the nuclei of neurons.
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Report
(3 results)
Research Products
(19 results)
