Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury.

Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. Research Abstract Details 

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Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. Abstract Text:

Rajesh Gopalrao Katare,Zou Zhitian,Mikiko Sodeoka,Shiro Sasaguri,Rajesh Gopalrao Katare,Zou Zhitian,Mikiko Sodeoka,Shiro Sasaguri,

Despite major advances in treating patients with coronary heart disease, reperfusion injury is still considered to be a major problem, especially in surgical settings. Here, we demonstrate the protective effects of a novel bisindolylmaleimide derivative, MS1 (2-[1-(3-aminopropyl)indol-3-yl]-3-(indol-3-yl)-N-methylmaleimide), against reperfusion injury of the heart. After anesthesia and artificial ventilation, Wistar rats were subjected to 30 min of left coronary artery occlusion followed by 120 min of reperfusion with or without treating the rats with MS1 (2.25 mumol.L-1.kg-1) before left coronary artery occlusion. Compared with the untreated hearts, MS1 treatment significantly reduced myocardial infarct size (35.1% +/- 3% vs. 75.5% +/- 5%, p < 0.001), reduced prevalence of apoptotic cells (2.6% +/- 0.5% vs. 12.2% +/- 2.1%, p < 0.001), prevented mitochondrial swelling and cytochrome c release, inhibited downregulation of antiapoptotic protein Bcl-2 expression, and suppressed caspase-3 activation. In contrast, pretreatment with atractyloside, a mitochondrial permeability transition pore opener, abolished the protective effects of MS1. In conclusion, MS1 inhibits pathologic opening of permeability transition pores and protects the heart against reperfusion injury and pathologic apoptosis.

Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. Publishing Authors By Initials

RG Katare,Z Zhitian,M Sodeoka,S Sasaguri,RG Katare,Z Zhitian,M Sodeoka,S Sasaguri,

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Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Canadian journal of physiology and pharmacology

VOLUME: 85

Page Numbers: 979-85

Journal Abbreviation: Can. J. Physiol. Pharmacol.

ISSN: 0008-4212

DAY: 10

MONTH: Oct

YEAR: 2007

Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury.

AFFILIATION: Department of Surgery II, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan.

Country: Canada

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MEDLINETA: Can J Physiol Pharmacol

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