Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.
Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.
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核仁素下调参与 ADP 诱导的 S 期细胞周期停滞和血管内皮细胞的细胞凋亡。
DOI：
10.1371/journal.pone.0110101
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Wang W;Luo J;Xiang F;Liu X;Jiang M;Liao L;Hu J
高浓度的胞外ADP已被报道可诱导细胞凋亡，但其分子机制尚未完全阐明。在本研究中，我们偶然发现ADP处理人脐静脉内皮细胞（HUVEC）和人主动脉内皮细胞（HAEC）后，核仁蛋白水平呈剂量依赖性和时间依赖性下调。ADP处理未降低核仁蛋白的转录水平，提示ADP可能诱导核仁蛋白降解。HUVEC和HAEC表达ADP受体P2Y13受体，但不表达P2Y1和P2Y12受体。然而，p2y1,12,13受体拮抗剂MRS2179， PSB0739， MRS2211不抑制adp诱导的核蛋白下调。此外，MRS2211本身下调核蛋白水平。此外，P2Y1、12和13受体的激动剂2-MeSADP不下调核蛋白。这些结果表明，adp诱导的核仁蛋白下调不是由于P2Y1、12或13受体的激活。我们还发现ADP通过下调核蛋白诱导细胞周期阻滞在S期，细胞凋亡和细胞增殖抑制。通过基因转移过表达核仁蛋白可部分逆转adp诱导的细胞周期阻滞、细胞凋亡和细胞增殖抑制。此外，ADP通过下调Bcl-2表达使HUVEC对顺铂诱导的细胞死亡增敏。综上所述，我们首次发现了一种新的机制，即ADP通过靶向核蛋白诱导细胞周期阻滞和细胞凋亡来调节细胞增殖。
High concentration of extracellular ADP has been reported to induce cell apoptosis, but the molecular mechanisms remain not fully elucidated. In this study, we found by serendipity that ADP treatment of human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells (HAEC) down-regulated the protein level of nucleolin in a dose- and time-dependent manner. ADP treatment did not decrease the transcript level of nucloelin, suggesting that ADP might induce nucleolin protein degradation. HUVEC and HAEC expressed ADP receptor P2Y13 receptor, but did not express P2Y1 or P2Y12 receptors. However, P2Y1, 12, 13 receptor antagonists MRS2179, PSB0739, MRS2211 did not inhibit ADP-induced down-regulation of nucleolin. Moreover, MRS2211 itself down-regulated nucleolin protein level. In addition, 2-MeSADP, an agonist for P2Y1, 12 and 13 receptors, did not down-regulate nucleolin protein. These results suggested that ADP-induced nucleolin down-regulation was not due to the activation of P2Y1, 12, or 13 receptors. We also found that ADP treatment induced cell cycle arrest in S phase, cell apoptosis and cell proliferation inhibition via nucleolin down-regulation. The over-expression of nucleolin by gene transfer partly reversed ADP-induced cell cycle arrest, cell apoptosis and cell proliferation inhibition. Furthermore, ADP sensitized HUVEC to cisplatin-induced cell death by the down-regulation of Bcl-2 expression. Taken together, we found, for the first time to our knowledge, a novel mechanism by which ADP regulates cell proliferation by induction of cell cycle arrest and cell apoptosis via targeting nucelolin.
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影响因子：
3.7
作者：
Hovanessian AG;Soundaramourty C;El Khoury D;Nondier I;Svab J;Krust B
通讯作者：
Krust B
影响因子：
5.4
作者：
Cancio-Lonches, Clotilde;Yocupicio-Monroy, Martha;Lorena Gutierrez-Escolano, Ana
通讯作者：
Lorena Gutierrez-Escolano, Ana
影响因子：
5.5
作者：
Lyubchenko, Taras;Woodward, Heather;Gerasimovskaya, Evgenia V.
通讯作者：
Gerasimovskaya, Evgenia V.
影响因子：
8.2
作者：
Amisten, S.;Meidute-Abaraviciene, S.;Erlinge, D.
通讯作者：
Erlinge, D.
影响因子：
20.3
作者：
Jin, JG;Quinton, TM;Kunapuli, SP
通讯作者：
Kunapuli, SP