PARASITE INDUCED CATABOLISM IN MAMMALS

哺乳动物的寄生虫和细菌入侵与许多 宿主常见的代谢紊乱 其中之一就是归纳 分解代谢状态，当延长时，可导致恶病质，休克和 死亡 我们最近分离出一种巨噬细胞产物，恶病质， 这是为了回应T。布氏杆菌、伯氏疟原虫和内毒素， 体内脂肪细胞脂蛋白脂酶的合成和3 T3-L1 体外前脂肪细胞。 随后分析了恶病质素对3 T3-L1细胞的作用， 表明，恶病质还抑制其他关键合成代谢的合成， 脂肪酸合成所必需的酶-乙酰辅酶A羧化酶， 脂肪酸合成酶 这些合成代谢酶的抑制是高度 选择性，因为用S35-甲硫氨酸加标记细胞揭示了 放射性结合到蛋白质中的一般模式是 不管有没有调解人 卡舍丁似乎是 免疫系统和身体其他细胞之间的通讯系统 参与能源储存和利用。 在本申请中，提出检查1）恶病质在本发明中的作用 可能处于恶病质状态， 与寄生虫，2）可能的生物学效应的恶病质对其他细胞 3）利用重组DNA技术克隆恶病质素。 这些研究提供了阐明一种致病性 在各种寄生虫病中常见的方式，这可能导致 融合治疗方法的发展。

Parasitic and bacterial invasion of mammals is associated with a number of common metabolic derangements of the host. One of these is the induction of a catabolic state which, when prolonged, can lead to cachexia, shock and death. We have recently isolated a macrophage product, cachectin, which is made in response to T. brucei, P. berghei, and endotoxin that inhibits the synthesis of the enzyme lipoprotein lipase of adipocytes in vivo and 3T3-L1 pre-adipocytes in vitro. Subsequent analysis of the effect of the cachectin on the 3T3-L1 cells has revealed that cachectin also inhibits the synthesis of other key anabolic enzymes essential for fatty acid synthesis-acetyl Co-A carboxylase and fatty acid synthetase. The inhibition of these anabolic enzymes is highly selective, since plus labeling of the cells with S35-methionine reveals that the general pattern of incorporation of radioactivity into protein is the same with or without the mediator. Cachetin appears to be part of a communication system between the immune system and other cells of the body involved in energy storage and utilization. In the current application it is proposed to examine 1) what role cachectin might have in the cachectic state commonly observed in animals infected with parasites, 2) possible biological effects of cachectin on other cell types and 3) the cloning of cachectin by recombinant DNA technology. These studies offer the possibility of elucidating a type of pathogenic modality common in a wide variety of parasitic diseases, which may lead to the development of convergent therapeutic approaches.