PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells
| Autor: | Ping Li, Xiaoshu Cheng, Xin Guo, Pingping Lei, Shoujun Shi, Shike Luo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Senescence
Apoptosis Biology medicine.disease_cause Ion Channels Cell Line Mitochondrial Proteins Proto-Oncogene Proteins c-myc Phosphatidylinositol 3-Kinases chemistry.chemical_compound Annexin Human Umbilical Vein Endothelial Cells Genetics medicine Humans Uncoupling Protein 2 Propidium iodide Telomerase Molecular Biology Protein kinase B Cellular Senescence PI3K/AKT/mTOR pathway Angiotensin II Endothelial Cells General Medicine Molecular biology Matrix Metalloproteinases Cell biology chemistry Tumor Suppressor Protein p53 Reactive Oxygen Species Proto-Oncogene Proteins c-akt Oxidative stress Signal Transduction |
| Zdroj: | Molecular Biology Reports. 41:6931-6937 |
| ISSN: | 1573-4978 0301-4851 |
| DOI: | 10.1007/s11033-014-3580-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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