Li W, Chou I N, Boak A, Kagan H M
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Am J Respir Cell Mol Biol. 1995 Oct;13(4):418-25. doi: 10.1165/ajrcmb.13.4.7546771.
Lysyl oxidase, a copper-dependent metalloenzyme, plays a central role in crosslinking of collagen and elastin in the extracellular matrix. Notably, lung lysyl oxidase activity is markedly stimulated in rats exposed to cadmium vapors. To further understand the mechanism of cadmium toxicity, the mRNA expression, synthesis, post-translational processing, and catalytic activity of lysyl oxidase were examined in cadmium-resistant (CdR) cells and the cadmium-sensitive Swiss mouse 3T3 cells from which they were derived. These CdR cells synthesized and accumulated markedly elevated levels of metallothionein, a known marker for cadmium resistance, whereas the expression of lysyl oxidase was reduced considerably. In comparison to the parental, cadmium-sensitive cells, the suppression of enzyme production in the CdR cells was seen at the mRNA level, at the levels of intracellular proprotein production and mature enzyme secreted into the medium, and in terms of total enzyme activity in the culture. The presence of cupric chloride in the culture medium during the incubation of the CdR cells for 16 h significantly enhanced lysyl oxidase activity accumulating in the medium, suggesting that lysyl oxidase deficiency in CdR cells may be related to abnormal copper metabolism.
赖氨酰氧化酶是一种依赖铜的金属酶，在细胞外基质中胶原蛋白和弹性蛋白的交联过程中起核心作用。值得注意的是，暴露于镉蒸气的大鼠肺中赖氨酰氧化酶活性受到显著刺激。为了进一步了解镉毒性的机制，研究了抗镉（CdR）细胞及其来源的镉敏感瑞士小鼠3T3细胞中赖氨酰氧化酶的mRNA表达、合成、翻译后加工及催化活性。这些CdR细胞合成并积累了显著升高水平的金属硫蛋白，这是一种已知的抗镉标志物，而赖氨酰氧化酶的表达则大幅降低。与亲本镉敏感细胞相比，CdR细胞中酶产生的抑制在mRNA水平、细胞内前体蛋白产生水平以及分泌到培养基中的成熟酶水平以及培养物中的总酶活性方面均可见。在CdR细胞孵育16小时期间，培养基中存在氯化铜可显著增强积累在培养基中的赖氨酰氧化酶活性，表明CdR细胞中赖氨酰氧化酶缺乏可能与异常的铜代谢有关。
