Zhang Baochun, Liu Ye, Harbrecht Brian G
Department of Surgery, University of Pittsburgh Medical Center, 3459 Fifth Avenue NW607, MUH, Pittsburgh, PA 15213, USA. zhangb+@pitt.edu
Nitric Oxide. 2003 Jun;8(4):262-5. doi: 10.1016/s1089-8603(03)00041-7.
We examined effects of cyclic AMP on adenovirus mediated inducible nitric oxide synthase expression in primary rat hepatocytes. In AdCMV-hiNOS infected hepatocytes, dbcAMP at a concentration of 1-100 microM inhibited nitrite and nitrate accumulation, iNOS protein and iNOS mRNA expression. At a concentration of 1-5mM, dbcAMP increased iNOS activity and expression. Both the inhibitory and stimulatory effects of cAMP on adenovirus mediated iNOS expression were dose dependent. This dual effect of cAMP on iNOS activity and expression can be accounted by its effect on CMV promoter activity since dbcAMP significantly inhibited CMV promoter activity in hepatocytes at low concentration and induced it at high concentration. We concluded that dbcAMP can regulate adenovirus-mediated human iNOS expression in primary hepatocytes by the mechanisms regulating the CMV promoter used in the adenovirus vector.
我们研究了环磷酸腺苷（cAMP）对腺病毒介导的原代大鼠肝细胞中诱导型一氧化氮合酶（iNOS）表达的影响。在感染了AdCMV-hiNOS的肝细胞中，浓度为1-100微摩尔的双丁酰环磷腺苷（dbcAMP）抑制了亚硝酸盐和硝酸盐的积累、iNOS蛋白和iNOS mRNA的表达。在浓度为1-5毫摩尔时，dbcAMP增加了iNOS的活性和表达。cAMP对腺病毒介导的iNOS表达的抑制和刺激作用均呈剂量依赖性。cAMP对iNOS活性和表达的这种双重作用可以通过其对巨细胞病毒（CMV）启动子活性的影响来解释，因为低浓度的dbcAMP显著抑制肝细胞中的CMV启动子活性，而高浓度时则诱导其活性。我们得出结论，dbcAMP可通过调节腺病毒载体中使用的CMV启动子的机制来调节原代肝细胞中腺病毒介导的人iNOS表达。
