Ioannidis I, Bätz M, Paul T, Korth H G, Sustmann R, De Groot H
Institut für Physiologische Chemie, Universitätsklinikum Essen, Germany.
Biochem J. 1996 Sep 15;318 ( Pt 3)(Pt 3):789-95. doi: 10.1042/bj3180789.
S-Nitroso-N-acetyl-DL-penicillamine (SNAP) and sodium nitroprusside (SNP), both of which are known to release nitric oxide (.NO), exhibited cytotoxicity against cultivated endothelial cells. Under hypoxic conditions 5 mM SNAP and 20 mM SNP induced a loss in cell viability of about 90% and 80% respectively, after an 8 h incubation. Under normoxic conditions, cell death was only 45% and 42% respectively within the same time period. Concentrations of .NO liberated from SNAP and SNP were measured by the oxyhaemoglobin method and by two of the recently developed nitric oxide cheletropic traps (NOCTs). The .NO concentrations from SNAP and SNP increased from 74 microM and 28 microM to 136 microM and 66 microM respectively within 15 min of hypoxic incubation, and then decreased to 36 microM and 28 microM. In the respective normoxic incubations the .NO levels from SNAP and SNP remained in the region of about 30 microM and 20 microM respectively. In contrast, spermine/NO adduct (spermineNONOate) was shown to be more toxic under normoxic than under hypoxic conditions. Under either of these conditions, the concentration of .NO liberated from 2 mM spermineNONOate was about 20 microM. The results demonstrate that the cytotoxicity of SNAP and SNP, but not of spermineNONOate, is significantly enhanced under hypoxic compared with normoxic incubations. Studies on the .NO-releasing behaviour of these compounds indicate that the increased toxicity of SNAP and SNP under hypoxic conditions is related to the influence of O2 on the chemical processes by which .NO is produced from the precursors, rather than to an increased sensitivity of the hypoxic cells towards .NO.
已知能释放一氧化氮（·NO）的亚硝基 - N - 乙酰 - DL - 青霉胺（SNAP）和硝普钠（SNP），对培养的内皮细胞表现出细胞毒性。在缺氧条件下，5 mM 的 SNAP 和 20 mM 的 SNP 分别在孵育 8 小时后导致细胞活力损失约 90% 和 80%。在常氧条件下，同一时间段内细胞死亡率分别仅为 45% 和 42%。通过氧合血红蛋白法以及两种最近开发的一氧化氮螯合捕集器（NOCTs）测量了从 SNAP 和 SNP 释放的·NO 浓度。缺氧孵育 15 分钟内，SNAP 和 SNP 的·NO 浓度分别从 74 μM 和 28 μM 增加到 136 μM 和 66 μM，然后降至 36 μM 和 28 μM。在各自的常氧孵育中，SNAP 和 SNP 的·NO 水平分别保持在约 30 μM 和 20 μM 范围内。相比之下，精胺/NO 加合物（精胺亚硝基铁氰化物）在常氧条件下比在缺氧条件下毒性更大。在这两种条件中的任何一种下，从 2 mM 精胺亚硝基铁氰化物释放的·NO 浓度约为 20 μM。结果表明，与常氧孵育相比，缺氧条件下 SNAP 和 SNP 的细胞毒性显著增强，而精胺亚硝基铁氰化物则不然。对这些化合物释放·NO 行为的研究表明，缺氧条件下 SNAP 和 SNP 毒性增加与 O2 对由前体产生·NO 的化学过程的影响有关，而不是与缺氧细胞对·NO 的敏感性增加有关。
