Department of Anesthesiology, China-Japan Union Hospital JiLin University, Chang Chun, JiLin, 130033, China.
Department of Vascular Surgery, China-Japan Union Hospital JiLin University, Chang Chun, JiLin, 130033, China.
Life Sci. 2019 Dec 15;239:116874. doi: 10.1016/j.lfs.2019.116874. Epub 2019 Sep 12.
Atherosclerosis (AS) is a chronic inflammatory disease that results from Oxidized low-density lipoprotein (Ox-LDL) induced endothelial dysfunction. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is closely related to the development of epithelial cells, but the role of CPEB1 in AS remains unknown. The RNA and protein levels of CPEB1 expression are increased by Ox-LDL exposure, which is abrogated by c-Jun amino-terminal kinase (JNK) inhibitor SP600125. CPEB1 small interfering RNA (siRNA) suppressed the oxidative stress, inflammation, and apoptosis. Furthermore, CPEB1 siRNA enhanced the sirtuin 1 (SIRT1) transcription levels in Ox-LDL-treated HUVECs. Co-Immunoprecipitation (Co-IP) assay showed that CPEB1 siRNA declined the ubiquitination of SIRT1, and SIRT1 siRNA enhanced the Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which were decreased by CPEB1 siRNA. In addition, LOX-1 and SIRT1 attenuated the protection of SIRT1 siRNA on Ox-LDL-induced oxidative stress. Therefore, our study revealed that CPEB1 depletion might play an anti-inflammatory and antiapoptotic role in Ox-LDL-induced apoptosis and inflammation though SIRT1/LOX-1 signalling pathway.
动脉粥样硬化（AS）是一种慢性炎症性疾病，由氧化型低密度脂蛋白（Ox-LDL）诱导的内皮功能障碍引起。细胞质多聚腺苷酸化元件结合蛋白 1（CPEB1）与上皮细胞的发育密切相关，但 CPEB1 在 AS 中的作用尚不清楚。CPEB1 的 RNA 和蛋白水平表达在 Ox-LDL 暴露下增加，这一增加被 c-Jun 氨基末端激酶（JNK）抑制剂 SP600125 所阻断。CPEB1 小干扰 RNA（siRNA）抑制氧化应激、炎症和细胞凋亡。此外，CPEB1 siRNA 增强了 Ox-LDL 处理的 HUVECs 中的沉默调节蛋白 1（SIRT1）转录水平。免疫共沉淀（Co-IP）检测显示 CPEB1 siRNA 降低了 SIRT1 的泛素化，而 SIRT1 siRNA 增强了凝集素样氧化型低密度脂蛋白受体-1（LOX-1），这两者均被 CPEB1 siRNA 降低。此外，LOX-1 和 SIRT1 减弱了 SIRT1 siRNA 对 Ox-LDL 诱导的氧化应激的保护作用。因此，我们的研究表明，CPEB1 耗竭可能通过 SIRT1/LOX-1 信号通路在 Ox-LDL 诱导的凋亡和炎症中发挥抗炎和抗凋亡作用。
