Inhibition of Sarcolemmal Carbon-Centered Free Radical Formation by Propranolo
Inhibition of Sarcolemmal Carbon-Centered Free Radical Formation by Propranolo
复制标题
普萘洛抑制肌膜碳中心自由基的形成
作者：
I. Mak;C. Arroyo;W. Weglicki
应用电子自旋共振自旋捕获技术，以5，5-二甲基-1-吡咯啉-N-氧化物（DMPO）和2-甲基-2-亚硝基丙烷（MNP）为靶分子，研究了心得安抑制心肌细胞膜脂质过氧化的机制。高纯度的犬肌细胞肌膜过氧化由超氧化物驱动（从二羟基富马酸盐）和Fe 3+催化的自由基产生系统。羟基自由基（-OH），确定由电子自旋共振信号DMPO-OH加合物，在水相中产生。高达500 μM的普萘洛尔不能有效降低DMPO-OH加合物的强度。当肌膜与MNP孵育前加入自由基，MNP加合物特征的碳中心的自由基产生。用普萘洛尔（3-100 μM）预处理膜，以对数浓度依赖性方式降低MNP加合物的强度; EC 50约为7 μM。发现D-和L-普萘洛尔同样有效。当蛋白质耗尽的肌膜脂质同样孵育MNP和自由基系统，相同的MNP加合物进行了观察，这一发现表明，加合物是脂质过氧化产生的脂质衍生产品。此外，它们的形成也受到普萘洛尔预处理的抑制。由于普萘洛尔不是水相中氧自由基的有效清除剂，因此数据表明普萘洛尔的抗过氧化作用是由于其与膜的亲脂性相互作用，从而随后中断自由基链反应。
The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl- 1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxidc-driven (from dihydroxyfumarate) and Fe3+-catalyzed free radical-generating system. Hydroxyl radicals (-OH), identified by electron spin resonance signals as DMPO-OH adducts, were generated in the aqueous phase. Propranolol up to 500 μM did not effectively reduce the intensity of the DMPO-OH adducts. When the sarcolemma were incubated with MNP before the addition of free radicals, MNP adducts characteristic of carbon-centered radicals were produced. Pretreatment of the membranes with propranolol (3-100 μM) decreased the intensity of the MNP adducts in a log concentrationdependent manner; the EC50 is about 7 μM. D- and L-propranolol were found equally effective. When protein-depleted sarcolemmal lipids were similarly incubated with MNP and the free radical system, identical MNP adducts were observed; this finding suggests that the adducts were lipid-derived products arising from lipid peroxidation. Furthermore, their formation was also inhibited by propranolol pretreatment. Since propranolol is not an effective scavenger of oxygen radicals in the aqueous phase, the data suggest that the antiperoxidative effect of propranolol is due to its lipophilic interaction with the membrane and thus subsequent interruption of the free radical chain reactions.
DOI：
10.1016/s0021-9258(17)43979-2
发表时间：
1983-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
I. Mak;H. Misra;W. Weglicki
通讯作者：
I. Mak;H. Misra;W. Weglicki
由于自由基，增强了溶酶体磷脂的降解和溶酶体磷脂的产生。
DOI：
10.1016/0006-291x(84)90941-0
发表时间：
1984
影响因子：
3.1
作者：
Weglicki,WB;Dickens,BF;Mak,IT
通讯作者：
Mak,IT