Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats

Takashi Horiguchi, Bela Kis, Nishadi Rajapakse, Katsuyoshi Shimizu, David W. Busija

研究成果: Article

77 引用 (Scopus)

抄録

Background and Purpose - The role of mitochondrial ATP-sensitive potassium channels (mitoKATP) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoKATP activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Methods - Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n = 16) or vehicle (saline; n = 16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n = 16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoKATP, we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 μmol/L 3-NPA-induced alterations of mitochondrial membrane potential (ΔΨm) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Results - Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of ΔΨm was completely blocked by 5-HD pretreatment. Conclusions - These results strongly suggest that opening of mitoKATP plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.

元の言語English
ページ(範囲)1015-1020
ページ数6
ジャーナルStroke
34
発行部数4
DOI
出版物ステータスPublished - 2003 4 1
外部発表Yes

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KATP Channels
Transient Ischemic Attack
Brain
Mitochondrial Membrane Potential
Middle Cerebral Artery
Neurotoxins
Neuroprotective Agents
3-nitropropionic acid
Fluorescent Dyes
Astrocytes
Reperfusion
Wistar Rats
Cultured Cells
Esters
5-hydroxydecanoic acid
mitochondrial K(ATP) channel
Neurons

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

これを引用

Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats. / Horiguchi, Takashi; Kis, Bela; Rajapakse, Nishadi; Shimizu, Katsuyoshi; Busija, David W.

:: Stroke, 巻 34, 番号 4, 01.04.2003, p. 1015-1020.

研究成果: Article

Horiguchi, Takashi ; Kis, Bela ; Rajapakse, Nishadi ; Shimizu, Katsuyoshi ; Busija, David W. / Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats. :: Stroke. 2003 ; 巻 34, 番号 4. pp. 1015-1020.
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abstract = "Background and Purpose - The role of mitochondrial ATP-sensitive potassium channels (mitoKATP) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoKATP activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Methods - Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n = 16) or vehicle (saline; n = 16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n = 16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoKATP, we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 μmol/L 3-NPA-induced alterations of mitochondrial membrane potential (ΔΨm) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Results - Treatment with 3-NPA exhibited a 16{\%} reduction (P<0.05) and 23{\%} reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of ΔΨm was completely blocked by 5-HD pretreatment. Conclusions - These results strongly suggest that opening of mitoKATP plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.",
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T1 - Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats

AU - Horiguchi, Takashi

AU - Kis, Bela

AU - Rajapakse, Nishadi

AU - Shimizu, Katsuyoshi

AU - Busija, David W.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Background and Purpose - The role of mitochondrial ATP-sensitive potassium channels (mitoKATP) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoKATP activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Methods - Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n = 16) or vehicle (saline; n = 16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n = 16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoKATP, we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 μmol/L 3-NPA-induced alterations of mitochondrial membrane potential (ΔΨm) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Results - Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of ΔΨm was completely blocked by 5-HD pretreatment. Conclusions - These results strongly suggest that opening of mitoKATP plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.

AB - Background and Purpose - The role of mitochondrial ATP-sensitive potassium channels (mitoKATP) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoKATP activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Methods - Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n = 16) or vehicle (saline; n = 16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n = 16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoKATP, we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 μmol/L 3-NPA-induced alterations of mitochondrial membrane potential (ΔΨm) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Results - Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of ΔΨm was completely blocked by 5-HD pretreatment. Conclusions - These results strongly suggest that opening of mitoKATP plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.

KW - Brain ischemia

KW - Middle cerebral artery occlusion

KW - Mitochondria

KW - Potassium channels

KW - Rats

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