SKELETAL-MUSCLE MITOCHONDRIAL PHOSPHOLIPASE-A2 AND THE INTERACTION OF MITOCHONDRIA AND SARCOPLASMIC-RETICULUM IN PORCINE MALIGNANT HYPERTHERMIA
SKELETAL-MUSCLE MITOCHONDRIAL PHOSPHOLIPASE-A2 AND THE INTERACTION OF MITOCHONDRIA AND SARCOPLASMIC-RETICULUM IN PORCINE MALIGNANT HYPERTHERMIA
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DOI：
10.1016/0005-2728(81)90183-3
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
CHEAH, AM
中科院分区：
文献类型：
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作者：
CHEAH, KS;CHEAH, AM
对遗传选择的恶性高热倾向猪和正常猪的背最长肌线粒体和肌浆网的 Ca2+ 转运系统进行了比较研究，以鉴定导致猪恶性高热发生的肌浆中 Ca2+ 释放增加的生化病变。从恶性高热倾向猪的背最长肌中分离的线粒体含有显着（P < 0.001）较高量的内源性长链脂肪酸。在两种类型的猪中观察到相似数量的内源性线粒体磷脂酶 A2，但易发生恶性高热的猪的总活性至少是正常猪的两倍。精胺是一种磷脂酶 A2 抑制剂，可将两种线粒体的活性降低至相似的最终水平。恶性高热倾向猪的线粒体表现出显着（P < 0.001）较高的寡霉素不敏感 (Ca2+ + Mg2+)-ATPase 活性，但两种类型猪的 Mg2+-ATPase 和 (Ca2+ + Mg2+)-ATPase 活性相似。从恶性高热倾向猪的背最长肌中分离的肌浆网显示出显着较高的 (Ca2+ + Mg2+)-ATPase 活性和较低的 Ca2+ 摄取率；恶性高热猪肌浆网对Ca2+的最大摄取量和摄取率均为正常猪的一半。恶性高热倾向猪背最长肌线粒体抑制正常和恶性高热倾向猪背最长肌肌浆网的Ca2+转运系统，但正常猪线粒体对这两种类型的肌浆网均没有影响。实验证据支持这一概念，即在猪恶性高热综合征期间，内源性线粒体磷脂酶 A2 从骨骼肌线粒体释放的长链脂肪酸负责线粒体中 Ca2+ 的释放增强，以及肌浆网中 Ca2+ 额外释放到肌浆中。
Comparative studies were carried out on the Ca2+-transport systems of mitochondria and sarcoplasmic reticulum from longissimus dorsi muscle of genetically selected malignant hyperthermia-prone and normal pigs to identify the biochemical lesion responsible for the enhanced release of Ca2+ in the sarcoplasm occurring in porcine malignant hyperthermia. Mitochondria isolated from longissimus dorsi muscle of malignant hyperthermiaprone pigs contained a significantly (P < 0.001) higher amount of endogenous long-chain fatty acids. Similar amounts of endogenous mitochondrial phospholipase A2 were observed in both types of pigs, but the total activity in malignant hyperthermia-prone pigs was at least twice that of normal. Spermine, a phospholipase A2 inhibitor, lowered the activity in both types of mitochondria to a similar final level. Mitochondria of malignant hyperthermia-prone pigs showed a significantly (P < 0.001) higher oligomycin-insensitive (Ca2+ + Mg2+)-ATPase activity, but the Mg2+-ATPase and the (Ca2+ + Mg2+)-ATPase activities were similar in both types of pigs. Sarcoplasmic reticulum isolated from longissimus dorsi muscle of malignant hyperthermia-prone pigs showed a significantly higher (Ca2+ + Mg2+)-ATPase activity and a lower rate of Ca2+ uptake; the maximal amount and the rate of Ca2+ uptake by sarcoplasmic reticulum of malignant hyperthermia-prone pigs were half that of normal. Mitochondria from longissimus dorsi muscle of malignant hyperthermia-prone pigs inhibited the Ca2+-transport system of the sarcoplasmic reticulum of longissimus dorsi from both normal and malignant hyperthermia-prone pigs, but mitochondria from normal pigs had no influence on the sarcoplasmic reticulum from either type. Experimental evidence favors the concept that long-chain fatty acids released from skeletal muscle mitochondria by endogenous mitochondrial phospholipase A2 are responsible for the enhanced release of Ca2+ from mitochondria and also additional release of Ca2+ from sarcoplasmic reticulum into the sarcoplasm during porcine malignant hyperthermia syndrome.