Arnelle D R, Day B J, Stamler J S
Division of Respiratory Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nitric Oxide. 1997 Feb;1(1):56-64. doi: 10.1006/niox.1996.0107.
Diethyl dithiocarbamate (DDC) has been used extensively as an inhibitor of CuZn superoxide dismutase (SOD) in the study of superoxide and nitric oxide. Addition of DDC to solutions of the endogenous NO adduct S-nitrosoglutathione (GSNO) causes a rapid decrease in GSNO with concomitant formation of nitrite, nitrate, disulfuram, oxidized glutathione, and mixed disulfide. Nitric oxide and superoxide appear to be produced in the process. Product formation is best explained by a radical mechanism in which S-nitrosation of DDC facilitates disulfide formation following homolytic cleavage. S-Nitrosocysteine and S-nitroso-N-acetylpenicillamine are likewise unstable in the presence of DDC. These findings may complicate interpretation of experiments in which DDC is used to alter NO-mediated responses. Some biological actions of DDC may result from SNO elimination rather than SOD inactivation. Moreover, apparent DDC-induced potentiation of superoxide effects may derive from O2- produced during the conversion of SNO to NO.
二乙基二硫代氨基甲酸盐（DDC）在超氧化物和一氧化氮的研究中被广泛用作铜锌超氧化物歧化酶（SOD）的抑制剂。向内源性NO加合物S-亚硝基谷胱甘肽（GSNO）溶液中添加DDC会导致GSNO迅速减少，同时生成亚硝酸盐、硝酸盐、双硫仑、氧化型谷胱甘肽和混合二硫化物。在此过程中似乎会产生一氧化氮和超氧化物。产物形成最好用自由基机制来解释，其中DDC的S-亚硝化作用促进了均裂裂解后二硫化物的形成。S-亚硝基半胱氨酸和S-亚硝基-N-乙酰青霉胺在DDC存在下同样不稳定。这些发现可能会使使用DDC改变NO介导反应的实验解释变得复杂。DDC的一些生物学作用可能是由于SNO消除而非SOD失活所致。此外，DDC诱导的超氧化物效应增强可能源于SNO转化为NO过程中产生的O2-。
