title: PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells.
abstract: Oxidative DNA damage contributes to replicative senescence. We explored the mechanism by which angiotensin II (Ang II) induces senescence in human vascular endothelial cells (HUVECs). Following weeklong incubation with Ang II, cell senescence, apoptosis, reactive oxygen species (ROS) content and mitochondrial membrane potential (MMP) were measured by β-galactosidase, annexin V/propidium iodide, DCFH-DA and rhodamine 123 staining, respectively. The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot. LY294002 was applied to inhibit PI3K/Akt signaling. Ang II induced HUVEC senescence and apoptosis, and increased ROS content and depolarization of MMP in a dose-dependent manner. Ang II further elevated protein levels of TERT from 0.006 ± 0.041 at baseline, to 0.480 ± 00.031 in the presence of 10 µM Ang II, UCP2 from 0.297 ± 0.051 to 2.512 ± 0.024, p-Akt from 0.012 ± 0.024 to 0.874 ± 0.015, c-myc from 0.521 ± 0.015 to 1.064 ± 0.025, and p53 from 0.035 ± 0.047 to 1.195 ± 0.029 (all P < 0.01, vs. baseline). LY294002 pre-treatment significantly alleviated Ang II-induced HUVEC senescence, and partly reversed the elevation of TERT, UCP2, p-Akt, c-myc and p53 protein levels. PI3K/Akt/UCP2 signaling may be involved in cell senescence and apoptosis induced by Ang II in HUVECs.
authors: Department of Cardiovascular, The Second Affiliated Hospital to Nanchang University, Nanchang, 330006, Jiangxi, China, lipingmed@163.com.
authors: Ping
authors: P
authors: Li
authors: Xin
authors: X
authors: Guo
authors: Pingping
authors: P
authors: Lei
authors: Shoujun
authors: S
authors: Shi
authors: Shike
authors: S
authors: Luo
authors: Xiaoshu
authors: X
authors: Cheng
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D020782:Matrix Metalloproteinases