Lazo J S, Lynch T J, McCallister J
Am Rev Respir Dis. 1986 Jul;134(1):73-8. doi: 10.1164/arrd.1986.134.1.73.
The interaction between bleomycin (BLM) and angiotensin-converting enzyme (ACE) from bovine lungs, serum, and cultured pulmonary artery endothelial cells was examined. ACE activity from all sources was inhibited by metal-free BLM but not by metal-complexed BLM. The metal-free deamide metabolite of BLM, which is nontoxic, also inhibited ACE activity from bovine endothelial cell homogenates and serum. Incubation of intact cultured pulmonary artery endothelial cells for 1 h with metal-free BLM produced a concentration-dependent inhibition of cellular ACE activity, which was persistent, lasting at least 24 h after drug removal. In addition, the enzyme activity released into the culture medium was decreased. The inhibition of cellular ACE activity occurred in the absence of (1) cell death as measured by dye exclusion, (2) inhibition of total protein synthesis as measured by [3H]leucine incorporation, and (3) decreased cellular enzyme content as assayed using a monoclonal antibody against the enzyme. These results indicate that a brief exposure of intact cultured pulmonary endothelial cells to BLM can produce direct and prolonged inhibition of ACE activity. The inhibition of ACE activity does not relate directly to cell death but rather appears to result from metal chelation by BLM.
研究了博来霉素（BLM）与牛肺、血清及培养的肺动脉内皮细胞中的血管紧张素转换酶（ACE）之间的相互作用。所有来源的ACE活性均受到无金属BLM的抑制，但不受金属络合BLM的抑制。无毒的BLM无金属脱酰胺代谢产物也抑制牛内皮细胞匀浆和血清中的ACE活性。用无金属BLM孵育完整的培养肺动脉内皮细胞1小时，可产生浓度依赖性的细胞ACE活性抑制，这种抑制是持续性的，在药物去除后至少持续24小时。此外，释放到培养基中的酶活性降低。细胞ACE活性的抑制发生在以下情况不存在时：（1）通过染料排除法测定的细胞死亡；（2）通过[3H]亮氨酸掺入法测定的总蛋白合成抑制；（3）使用针对该酶的单克隆抗体测定的细胞酶含量降低。这些结果表明，完整的培养肺内皮细胞短暂暴露于BLM可产生直接且持久的ACE活性抑制。ACE活性的抑制与细胞死亡无直接关系，而似乎是由BLM的金属螯合作用导致的。
