Waalkes M P, Perantoni A, Palmer A E
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21701.
Biochem J. 1988 Nov 15;256(1):131-7. doi: 10.1042/bj2560131.
The mammalian testes are generally quite susceptible to cadmium. A deficiency of metallothionein (MT), a metal-binding protein linked to Cd tolerance, has been observed in rat testes and may explain the sensitivity in rats. Little is known about the metal-binding proteins in primate testes. Thus this study examined the nature of these proteins in a non-human primate species, the patas monkey (Erythrocebus patas). In all cases proteins isolated from testes were compared with authentic MT isolated from the liver of a zinc-treated monkey. A low-molecular-mass Zn/Cd-binding protein was seen in testicular and hepatic cytosol after gel filtration. Neither protein had substantial amounts of associated copper. These proteins could be partially purified from both sources by heat treatment and acetone precipitation. When such extracts were further separated by reverse-phase h.p.l.c., four hepatic forms were isolated, all of which proved to be authentic MT by amino acid analysis. However, only two testicular forms were separated by h.p.l.c., both of which had amino acid compositions quite unlike that of MT, having a much lower cysteine content and amino acids which are absent from MT (leucine and phenylalanine). The testicular protein appeared to be uninducible by Zn treatment. These results suggest that the low-molecular-mass Cd/Zn-binding proteins in the patas testes are not MTs and further support the hypothesis that a MT deficiency may be an important determinate of the marked testicular sensitivity to Cd toxicity.
哺乳动物的睾丸通常对镉相当敏感。在大鼠睾丸中已观察到金属硫蛋白（MT）缺乏，MT是一种与镉耐受性相关的金属结合蛋白，这可能解释了大鼠的敏感性。关于灵长类动物睾丸中的金属结合蛋白知之甚少。因此，本研究在一种非人类灵长类动物——赤猴（Erythrocebus patas）中研究了这些蛋白的性质。在所有情况下，将从睾丸中分离的蛋白与从经锌处理的猴子肝脏中分离的纯MT进行比较。凝胶过滤后，在睾丸和肝细胞溶胶中均可见到一种低分子量的锌/镉结合蛋白。两种蛋白均无大量相关铜。这些蛋白可通过热处理和丙酮沉淀从两种来源进行部分纯化。当用反相高效液相色谱进一步分离此类提取物时，分离出四种肝脏形式，通过氨基酸分析证明它们均为纯MT。然而，通过高效液相色谱仅分离出两种睾丸形式，它们的氨基酸组成与MT完全不同，半胱氨酸含量低得多，且含有MT中不存在的氨基酸（亮氨酸和苯丙氨酸）。睾丸蛋白似乎不受锌处理的诱导。这些结果表明，赤猴睾丸中的低分子量镉/锌结合蛋白不是MT，进一步支持了MT缺乏可能是睾丸对镉毒性明显敏感的一个重要决定因素的假说。
