PLC/CAMK IV-NF-kappaB 参与人内皮细胞中晚期糖基化终产物受体介导的信号通路。
PLC/CAMK IV-NF-kappaB involved in the receptor for advanced glycation end products mediated signaling pathway in human endothelial cells.
机构信息
Research Center of Molecular Medicine, Fujian Medical University, No. 88 Jiaotong Road, Fuzhou, Fujian 350004, PR China.
出版信息
Mol Cell Endocrinol. 2010 May 14;320(1-2):111-7. doi: 10.1016/j.mce.2010.01.036. Epub 2010 Feb 18.
Advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE) play an important role in diabetic vascular complications. The current study demonstrated that AGEs significantly increased RAGE expression and the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) in human umbilical vein endothelial cell-derived line ECV304 cells. RAGE antisense RNA partially inhibited the expression of TNF-alpha and IL-6 induced by AGEs. Oligonucleotide microarray was used to identify the genes that respond to RAGE activation. Phospholipase C beta 1 (PLC beta 1), phospholipase C beta 4 (PLC beta 4) and calcium/calmodulin-dependent protein kinase IV (CAMK IV) which associated with Ca(2+) signaling were upregulated. The rise of intracellular calcium and the NF-kappaB promoter activity induced by AGEs were suppressed by RAGE antisense RNA, PLC inhibitor U73122 and dominant negative CAMK IV, respectively. These findings suggest that PLC/CAMK IV-NF-kappaB is involved in RAGE mediated signaling pathway in human endothelial cells.
糖基化终产物（AGEs）及其与晚期糖基化终产物受体（RAGE）的相互作用在糖尿病血管并发症中起着重要作用。本研究表明，AGEs 可显著增加人脐静脉内皮细胞衍生系 ECV304 细胞中 RAGE 的表达和肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）的释放。RAGE 反义 RNA 部分抑制了 AGEs 诱导的 TNF-α和 IL-6 的表达。寡核苷酸微阵列用于鉴定对 RAGE 激活有反应的基因。与 Ca2+信号相关的磷酸脂酶 Cβ1（PLCβ1）、磷酸脂酶 Cβ4（PLCβ4）和钙/钙调蛋白依赖性蛋白激酶 IV（CAMK IV）被上调。AGEs 诱导的细胞内钙升高和 NF-κB 启动子活性分别被 RAGE 反义 RNA、PLC 抑制剂 U73122 和显性失活的 CAMK IV 抑制。这些发现表明，PLC/CAMK IV-NF-κB 参与了人内皮细胞中 RAGE 介导的信号通路。
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