Richter W O, Jacob B G, Schwandt P
Department of Medicine II, University of Munich, F.R.G.
Mol Cell Endocrinol. 1990 Jul 9;71(3):229-38. doi: 10.1016/0303-7207(90)90028-7.
beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
β-促脂解素是一种垂体肽，是兔脂肪组织中脂肪分解的强力刺激物。已表明这种多肽可被兔完整的脂肪垫、匀浆脂肪组织和脂肪细胞降解，其降解程度取决于脂肪组织的量、时间以及孵育介质的pH值。在兔脂肪细胞的亚细胞组分中，蛋白水解活性可定位于胞质溶胶和微粒体组分中。为了获得关于β-促脂解素在其靶细胞中加工过程的信息，在存在不同细胞机制抑制剂以及处于肥胖和饥饿等不同生理状态下，研究了该多肽的脂解和降解情况。因此，与瘦兔和饥饿兔相比，肥胖兔和随意进食动物的脂肪细胞中更强的脂解反应伴随着降解的显著增加。六种溶酶体促渗剂（氯喹、氯化铵、普萘洛尔、喹吖因、吖啶橙和丁卡因）、蛋白酶抑制剂α2-巨球蛋白和单丹磺酰尸胺、2-脱氧-D-葡萄糖和2,4-二硝基苯酚导致的细胞ATP耗竭以及孵育介质中Ca2+离子的缺失，均剂量依赖性地抑制完整和匀浆脂肪组织中的脂解活性以及β-促脂解素的降解。细胞骨架抑制剂如秋水仙碱、细胞松弛素B、长春碱和伴刀豆球蛋白A也降低了脂解，但仅降低了完整脂肪组织中的降解。可以得出结论，在受体介导的摄取后，细胞骨架和溶酶体蛋白酶参与了β-促脂解素的加工过程。
