The Korean Journal of Pharmacology (대한약리학회지)
- Volume 21 Issue 2
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- Pages.79-89
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- 1985
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- 0377-9459(pISSN)
A Study on the Mechanism of Calcium Binding Inhibition of Cardiac Sarcoplasmic Reticulum by Oxygen Free Radicals
산소대사물에 의한 심장근 Sarcoplasmic reticulum의 칼슘운반 억제 기전에 관한연구
- Kim, Hae-Won (Department of Pharmacology, College of Medicine, Seoul National University) ;
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Chung, Myung-Hee
(Department of Pharmacology, College of Medicine, Seoul National University) ;
- Kim, Myung-Suk (Department of Pharmacology, College of Medicine, Seoul National University) ;
- Park, Chan-Woong (Department of Pharmacology, College of Medicine, Seoul National University)
- Published : 1985.12.30
Abstract
Mechanism of calcium transport inhibition of cardiac sarcoplasmic reticulum (SR) by oxygen free radicals was examined. Effects of oxygen free radicals generated by xanthine/xanthine oxidase (X/XO) system on isolated porcine ventricle SR were studied with respect to its calcium binding, lipid peroxidation, SH-group content and alteration of membrane protein components. The results are as follows. 1) Calcium binding of isolated SR was markedly inhibited by X/XO. 2) During the incubation of sarcoplasmic reticulum with xanthine/xanthine oxidase, there were marked inclose in lipid peroxidation and reduction of SH-group content. 3) An antioxidant, p-phenylenediamine effectively prevented the lipid peroxidation but partially prevented the calcium binding inhibition of X/XO treated SR. 4) The reduction of SH-group content of SR treated with X/XO was partially prevented by p-phenylendiamine. 5) When modifying SH-group of SR by treatment with DTNB, the inhibition of calcium binding activity was partially prevented. 6) On gel-permeation chromatography of X/XO-treated sarcoplasmic reticulum, there was an increase of small molecular weight products, probably protein degradation products. 7) Semicarbazide, which prevents the cross-linking reaction of protein components, did not affect the calcium binding inhibition of X/XO-treated SR. From these results, it is suggested that the inhibition of calcium binding of SR by oxygen free radicals results from the consequence of multiple changes of SR components, which are lipid peroxidation, SH-group oxidation and degradation of protein components.
심근 세포의 칼슘 조절에 중요한 역할을 하는 sarcoplasmic reticulum (SR)의 칼슘운반 능력이 허혈 심근에서 현저히 억제됨이 알려져 있다. 이와같은 허혈 심근에서의 SR 칼슘운반승력 저하에 유독성 산소 대사물이 관여할 것으로 생각되고 있으나 그 기전에 관하여는 아직 알려진 바 없다. 본 연구에서는 그 기전의 일단을 규명하기 위하여 산틴 산화효소계에 의하여 발생된 유독성 산소대사물긴 돼지 심실근에서 추출한 sarcoplasmic reticulum의 칼슘흡수 및 막지질 과산화, sulfhydryl group 그리고 단백질 변성에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. 1) 산틴 산화 효소계와 반응시킨 sarcopl smic reticulum의 칼슘흡수는 반응시간 경과에 따라 현저히 억제되었다. 2) sarcoplasmic reticulum 막지질 과산화는 산딘 산화 효소계에 의하여 현저히 증가되었다 3) 항산화제