Ravichandran L V, Johns R A
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
FEBS Lett. 1995 Oct 30;374(2):295-8. doi: 10.1016/0014-5793(95)01134-z.
In this study, the role of cyclic GMP, the end product of the NO-cyclic GMP signalling pathway, in the regulation of ecNOS was investigated. Bovine pulmonary endothelial cells were exposed to 8-bromo-cyclic GMP and its effect on NO production, ecNOS protein, and mRNA levels was analyzed. Endothelial cells on exposure to 8-bromo-cyclic GMP produced significantly increased amounts of NO, detected as increased cyclic GMP in cocultures with vascular smooth muscle cells both under basal conditions and with agonist stimulation. 8-Bromo-cyclic GMP significantly increased the ecNOS protein and mRNA levels as detected on Western and Northern blots respectively. This 8-bromo-cyclic GMP mediated increase of NO production, ecNOS protein and mRNA levels suggests that cyclic GMP up-regulates the expression of ecNOS. Thus, there may be an intercellular feedback mechanism involved at the molecular level in the expression of the NO-cyclic GMP signalling pathway in blood vessels.
在本研究中,对一氧化氮-环磷酸鸟苷(NO-环磷酸鸟苷)信号通路的终产物环磷酸鸟苷在血管内皮型一氧化氮合酶(ecNOS)调节中的作用进行了研究。将牛肺内皮细胞暴露于8-溴环磷酸鸟苷,并分析其对一氧化氮生成、ecNOS蛋白和mRNA水平的影响。内皮细胞暴露于8-溴环磷酸鸟苷后,无论是在基础条件下还是在激动剂刺激下,与血管平滑肌细胞共培养时,检测到的环磷酸鸟苷增加,表明一氧化氮生成显著增加。8-溴环磷酸鸟苷分别在蛋白质免疫印迹法(Western blot)和Northern印迹法中显著增加了ecNOS蛋白和mRNA水平。这种由8-溴环磷酸鸟苷介导的一氧化氮生成、ecNOS蛋白和mRNA水平的增加表明,环磷酸鸟苷上调了ecNOS的表达。因此,在血管中NO-环磷酸鸟苷信号通路的表达在分子水平上可能存在一种细胞间反馈机制。