RRC ID |
2802
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著者 |
Yonemochi H, Ichinose M, Anan F, Taniguti Y, Shinohara T, Takahashi N, Nakagawa M, Saikawa T.
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タイトル |
Diazoxide-induced cardioprotection via DeltaPsim loss depending on timing of application.
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ジャーナル |
Life Sci
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Abstract |
Although the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in cardioprotection is widely accepted, it remains unclear when their opening is critical for protection. We tested the hypothesis that the mitoKATP channel acts as a trigger or mediator of protection against apoptosis through loss of mitochondrial inner membrane potential (DeltaPsim). Exposure of neonatal rat cardiomyocytes to H2O2 (0.5 mmol/L) resulted in apoptosis associated with severe DeltaPsim loss. Pretreatment with diazoxide (20 to 100 micromol/L) prevented H2O2-induced apoptosis and DeltaPsim loss at 2 but not 18 h after exposure, while the latter was prevented by cotreatment with diazoxide. Lack of protection by pretreatment with diazoxide was observed in cardiomyocytes cultured in a medium containing H2O2 for 2 h and then not containing for 16 h. The slopes of the regression lines of the relationship between the proportion of apoptotic cells and DeltaPsim loss (y = -0.89 vs. -0.42) and the proportion of cells with high side scatter signal differed between cardiomyocytes exposed H2O2 for 2 and 18 h. Diazoxide per se caused a transient DeltaPsim loss (within 30 min) with a recovery followed by persistent DeltaPsim loss (after 6 h). Inhibition of the former by 5-hydroxydecanoate (5-HD, 0.5 mmol/L) abolished protection of pretreatment with diazoxide (trigger phase), while that of the latter prevented the protection of cotreatment with diazoxide (mediator phase). Our results suggest that mitoKATP channels act as a trigger and mediator of cardioprotection through a transient or persistent DeltaPsim loss depending on phenotypic consequence in response to oxidants.
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巻・号 |
79(20)
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ページ |
1906-12
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公開日 |
2006-10-12
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DOI |
10.1016/j.lfs.2006.06.012
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PII |
S0024-3205(06)00463-2
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PMID |
16815475
|
MeSH |
Animals
Apoptosis / drug effects*
Cardiotonic Agents / pharmacology*
Decanoic Acids / pharmacology
Diazoxide / pharmacology*
Hydrogen Peroxide / toxicity
Hydroxy Acids / pharmacology
Membrane Potentials / drug effects
Mitochondria, Heart / drug effects
Mitochondria, Heart / physiology
Mitochondrial Membranes / drug effects*
Mitochondrial Membranes / physiology
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / physiology
Potassium Channels / drug effects
Potassium Channels / physiology*
Rats
Rats, Wistar
Time Factors
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IF |
3.647
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引用数 |
5
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WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
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リソース情報 |
ラット |
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