Baudry M, Simonson L, Dubrin R, Lynch G
J Neurobiol. 1986 Jan;17(1):15-28. doi: 10.1002/neu.480170103.
Recent studies have shown that soluble calcium activated proteases (calpains) in brain degrade proteins associated with the cytoskeleton and vary markedly in activity across regions and as a function of development. It was suggested that the observed differences in calpain activity reflect differences in the turnover rate of structural elements. The present study extends this analysis by measuring the properties and activity of calpain in representatives of the five classes of vertebrates with particular emphasis on the mammals. No evidence for proteolysis was found in soluble fractions of fish brains at neutral pH in the presence or absence of added calcium. A substantial calcium-independent proteolytic activity was found in amphibian brains--the effects of a variety of protease inhibitors indicated that it is also a neutral thiol (cysteine) protease. Reptilian brains exhibited both calcium-independent and calcium-dependent proteolytic activity. Virtually all proteolytic activity in birds (5 species) and mammals (9 species) measured at neutral pH was calcium-dependent. The endogenous substrates for the calcium activated proteases were very similar in several species of birds and mammals as were the effects of a variety of protease inhibitors. However, the activity of the enzyme, expressed per mg of soluble protein, was highly and negatively correlated with brain size in the mammals. The allometric expression for this relationship was similar to that found for the density of neurons in cerebral cortex as a function of absolute brain size. These results indicate that soluble proteolytic enzymes in brain are differentially expressed among classes of vertebrates and suggest that the turnover of cytoskeletal elements in birds and mammals differs in important ways from that found in fish and amphibians. The results obtained for mammals raise the possibility of a relationship between brain size and the rate at which structural elements are broken down and replaced in this vertebrate class.
最近的研究表明，大脑中的可溶性钙激活蛋白酶（钙蛋白酶）会降解与细胞骨架相关的蛋白质，其活性在不同脑区以及随发育进程有显著差异。有人提出，所观察到的钙蛋白酶活性差异反映了结构成分周转率的差异。本研究通过测量五类脊椎动物代表中钙蛋白酶的特性和活性来扩展这一分析，尤其着重于哺乳动物。在中性pH条件下，无论添加或不添加钙，在鱼脑的可溶性组分中均未发现蛋白水解的证据。在两栖动物大脑中发现了大量不依赖钙的蛋白水解活性——多种蛋白酶抑制剂的作用表明它也是一种中性硫醇（半胱氨酸）蛋白酶。爬行动物大脑表现出不依赖钙和依赖钙的蛋白水解活性。在中性pH条件下测量的鸟类（5种）和哺乳动物（9种）的几乎所有蛋白水解活性均依赖钙。几种鸟类和哺乳动物中钙激活蛋白酶的内源性底物非常相似，多种蛋白酶抑制剂的作用也是如此。然而，以每毫克可溶性蛋白表示的该酶活性在哺乳动物中与脑大小呈高度负相关。这种关系的异速生长表达式与大脑皮层神经元密度随绝对脑大小变化的表达式相似。这些结果表明，大脑中的可溶性蛋白水解酶在脊椎动物类别中存在差异表达，这表明鸟类和哺乳动物中细胞骨架成分的周转在重要方面不同于鱼类和两栖动物。在哺乳动物中获得的结果增加了脑大小与该脊椎动物类别中结构成分分解和替换速率之间存在关联的可能性。
