Polte T, Oberle S, Schröder H
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle (Saale), Germany.
FEBS Lett. 1997 Jun 2;409(1):46-8. doi: 10.1016/s0014-5793(97)00480-8.
In cultured endothelial cells, incubation with TNF-alpha (50 ng/ml) for 48 h markedly reduced viability of endothelial cells. A 6 h preincubation with Sper/NO (0.03--1 microM) protected endothelial cells in a concentration-dependent manner and increased viability by 63% of control. The NO scavenger PTIO (30 microM) completely abolished cytoprotection by Sper/NO. A cytoprotective effect comparable to Sper/NO was observed when preincubating the cells with 8-bromo cyclic GMP (1-10 microM). Moreover, no protection by Sper/NO occurred in the presence of ODQ (0.1 microM), a selective inhibitor of soluble guanylyl cyclase. Our results demonstrate that NO produces a long-term endothelial protection against cellular injury by TNF-alpha, presumably via a cyclic GMP-dependent pathway.
在培养的内皮细胞中，用肿瘤坏死因子-α（TNF-α，50纳克/毫升）孵育48小时可显著降低内皮细胞的活力。用精胺/一氧化氮（Sper/NO，0.03 - 1微摩尔）预孵育6小时以浓度依赖的方式保护内皮细胞，使活力比对照组提高63%。一氧化氮清除剂亚硝基铁氰化钠（PTIO，30微摩尔）完全消除了Sper/NO的细胞保护作用。当用8-溴环鸟苷酸（8-bromo cyclic GMP，1 - 10微摩尔）预孵育细胞时，观察到了与Sper/NO相当的细胞保护作用。此外，在可溶性鸟苷酸环化酶的选择性抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，0.1微摩尔）存在的情况下，Sper/NO没有产生保护作用。我们的结果表明，一氧化氮可能通过环鸟苷酸依赖性途径对肿瘤坏死因子-α引起的细胞损伤产生长期的内皮保护作用。
