Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.
Mol Cell Biochem. 2010 Apr;337(1-2):159-66. doi: 10.1007/s11010-009-0295-y. Epub 2009 Oct 23.
Endothelium-derived nitric oxide (NO) is a cytoprotective molecule to prevent endothelial cells (ECs) from apoptosis. CREB-binding protein (CBP) is involved in the apoptotic pathway in several tumor cells, however, little is known whether CBP is associated with apoptosis in ECs and the apoptotic effect of CBP on ECs is regulated by NO. Therefore, the purpose of the present study was to investigate whether silencing CBP expression could affect the sensitivity of ECs toward apoptotic stimuli and determined the role of NO. In this study, we found that when CBP expression was silenced by RNA interference, ECs were more prone to apoptosis under serum deprivation, whereas the apoptosis was not significantly induced in the serum-containing condition. The increased apoptosis is paralleled by a reduction of NO, and the apoptosis was reversed by NO donors, suggesting an important role of NO. Furthermore, CBP silencing decreased NO production by downregulating the endothelial NO synthase (eNOS) expression in a dose-dependent manner. These results indicated that CBP silencing is associated with decreased eNOS expression and NO production, and therefore concomitantly increased the sensitivity of ECs toward apoptosis.
内皮细胞衍生的一氧化氮 (NO) 是一种细胞保护分子，可防止内皮细胞 (ECs) 凋亡。CREB 结合蛋白 (CBP) 参与多种肿瘤细胞的凋亡途径，然而，尚不清楚 CBP 是否与 ECs 的凋亡有关，以及 NO 是否调节 CBP 对 ECs 的凋亡作用。因此，本研究旨在探讨沉默 CBP 表达是否会影响 ECs 对凋亡刺激的敏感性，并确定 NO 的作用。在这项研究中，我们发现当 CBP 表达被 RNA 干扰沉默时，ECs 在血清剥夺下更容易发生凋亡，而在含血清的条件下则不会明显诱导凋亡。增加的凋亡与 NO 的减少平行，而 NO 供体可逆转凋亡，表明 NO 的重要作用。此外，CBP 沉默通过下调内皮型一氧化氮合酶 (eNOS) 的表达以剂量依赖的方式减少 NO 的产生。这些结果表明，CBP 沉默与 eNOS 表达和 NO 产生减少有关，因此同时增加了 ECs 对凋亡的敏感性。
