Sumi D, Hayashi T, Jayachandran M, Iguchi A
Department of Geriatrics, Nagoya University Graduate School of Medicine, Japan.
Life Sci. 2001 Aug 24;69(14):1651-60. doi: 10.1016/s0024-3205(01)01251-6.
17beta-estradiol up-regulates endothelial nitric oxide synthase (eNOS) expression in cultured endothelial cells. To clarify the role of mRNA stabilization in upregulation of eNOS expression, endothelial cells were incubated with actinomycin D as transcriptional inhibitor. Up to 10 hours incubation with 17beta-estradiol alone did not affect significantly the stability of eNOS mRNA. As tumor necrosis factor-alpha (TNF-alpha) is associated with the progression of atherosclerosis, we examined the effect of 17beta-estradiol on eNOS mRNA destabilization with TNF-alpha. After 10 hours co-incubation with TNF-alpha, relative intensity of eNOS mRNA decreased to 50% of the intensity at the start time of incubation, however, it remained significantly 1.6 times in the presence of 17beta-estradiol. This inhibitory effect of 17beta-estradiol was abolished by the treatment of estrogen receptor antagonist, ICI 182,780. This is the first finding that 17beta-estradiol stabilizes eNOS mRNA destabilized by TNF-alpha through estrogen receptor mediated mechanism.
17β-雌二醇可上调培养的内皮细胞中内皮型一氧化氮合酶（eNOS）的表达。为阐明mRNA稳定性在eNOS表达上调中的作用，将内皮细胞与放线菌素D（一种转录抑制剂）一起孵育。单独用17β-雌二醇孵育长达10小时对eNOS mRNA的稳定性没有显著影响。由于肿瘤坏死因子-α（TNF-α）与动脉粥样硬化的进展相关，我们研究了17β-雌二醇对TNF-α导致的eNOS mRNA去稳定化的影响。与TNF-α共同孵育10小时后，eNOS mRNA的相对强度降至孵育开始时强度的50%，然而，在存在17β-雌二醇的情况下，其仍显著为原来的1.6倍。17β-雌二醇的这种抑制作用被雌激素受体拮抗剂ICI 182,780处理所消除。这是首次发现17β-雌二醇通过雌激素受体介导的机制稳定由TNF-α去稳定化的eNOS mRNA。
