Spiecker M, Darius H, Kaboth K, Hübner F, Liao J K
Cardiovascular Division, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Leukoc Biol. 1998 Jun;63(6):732-9.
Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression, their inhibitory effects on nuclear factor kappaB (NF-kappaB) activation may differ. The NO donors, but not 8-bromo-cGMP, decreased tumor necrosis factor alpha (TNF-alpha)-induced VCAM-1, ICAM-1, and E-selectin expression by 11-70%. In contrast, NAC completely abolished VCAM-1 and E-selectin expression and decreased ICAM-1 expression by 56%. Gel shift assays demonstrate that NF-kappaB activation was inhibited by both NO and antioxidants. The activation of NF-kappaB involves the phosphorylation and degradation of its cytoplasmic inhibitor IkappaB-alpha by 26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of phosphorylated IkappaB-alpha. NAC inhibited IkappaB kinase (IKK) activity and prevented IkappaB-alpha phosphorylation and degradation. In contrast, NO did not inhibit IKK activity, IkappaB-alpha phosphorylation, or IkappaB-alpha degradation. However, NO, but not antioxidants, induced IkappaB-alpha promoter activity. The inhibitory effects of NO on adhesion molecule expression, therefore, differs from that of antioxidants in terms of the mechanism by which NF-kappaB is inactivated.
尽管一氧化氮（NO）和抗氧化剂可抑制黏附分子的表达，但它们对核因子κB（NF-κB）激活的抑制作用可能有所不同。NO供体可使肿瘤坏死因子α（TNF-α）诱导的血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和E-选择素的表达降低11%-70%，而8-溴环鸟苷酸（8-bromo-cGMP）则无此作用。相比之下，N-乙酰半胱氨酸（NAC）可完全消除VCAM-1和E-选择素的表达，并使ICAM-1的表达降低56%。凝胶迁移试验表明，NO和抗氧化剂均能抑制NF-κB的激活。NF-κB的激活涉及到其胞质抑制剂IκB-α被26S蛋白酶体磷酸化和降解。26S蛋白酶体抑制剂MG132可阻止磷酸化IκB-α的降解。NAC可抑制IκB激酶（IKK）的活性，并阻止IκB-α的磷酸化和降解。相反，NO并不抑制IKK的活性、IκB-α的磷酸化或IκB-α的降解。然而，NO可诱导IκB-α启动子的活性，而抗氧化剂则无此作用。因此，NO对黏附分子表达的抑制作用在NF-κB失活机制方面与抗氧化剂不同。
