Govers Roland, de Bree Petra, Rabelink Ton J
Department of Vascular Medicine, UMC Utrecht, Utrecht, The Netherlands.
Life Sci. 2003 Sep 12;73(17):2225-36. doi: 10.1016/s0024-3205(03)00644-1.
Nitric oxide originating from the endothelial cells of the vessel wall is essential for the vascular system. It is produced by the enzyme endothelial nitric oxide synthase (eNOS). Cellular eNOS activity is affected by changes in eNOS synthesis. To address whether degradation also contributes to eNOS activity, the effect of proteasome inhibitors on eNOS-mediated NO synthesis was studied in the microvascular endothelial cell line bEnd.3 and in cultured primary aortic endothelial cells. Surprisingly, agonist-induced increases in eNOS activity were reduced to 42 and 50% in the presence of the proteasome inhibiting drugs MG132 and clasto-lactacystin-beta-lactone, respectively (P < 0.01). The decrease in activity occurred within 1 hour of drug treatment and was not accompanied by a change in intracellular levels of either eNOS or its inhibitor caveolin-1. Taken together, these data may indicate that eNOS is regulated by an interacting protein, different from caveolin-1, that inhibits its activity and is rapidly degraded by the proteasome in the presence of eNOS agonists.
源自血管壁内皮细胞的一氧化氮对血管系统至关重要。它由内皮型一氧化氮合酶（eNOS）产生。细胞内eNOS的活性受eNOS合成变化的影响。为了探究降解是否也对eNOS活性有影响，研究了蛋白酶体抑制剂对微血管内皮细胞系bEnd.3和原代培养的主动脉内皮细胞中eNOS介导的一氧化氮合成的作用。令人惊讶的是，在蛋白酶体抑制药物MG132和clasto- lactacystin-beta-lactone存在的情况下，激动剂诱导的eNOS活性增加分别降至42%和50%（P < 0.01）。药物处理1小时内活性就出现下降，且细胞内eNOS及其抑制剂小窝蛋白-1的水平均未发生变化。综上所述，这些数据可能表明，eNOS受一种与小窝蛋白-1不同的相互作用蛋白调节，该蛋白抑制eNOS的活性，并且在eNOS激动剂存在的情况下会被蛋白酶体迅速降解。
