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- W2070177458 abstract "To examine the effect of atorvastatin on homocysteine (Hcy)-induced reactive oxygen species (ROS) production and apoptosis in human umbilical vein endothelial cells (HUVECs).HUVECs were cultured with Hcy (0.1-5 mmol/L) in the presence or absence of atorvastatin (1-100 micromol//L) or various stress signaling inhibitors, including the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI, 10 micromol/L), the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 (10 micromol/L) and antioxidants N-acetyl cysteine (NAC, 1 mmol/L). Cell apoptosis was evaluated by Annexin V/propidium iodide staining and flow cytometry. ROS were detected by 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFH-DA). NADPH oxidases were evaluated with lucigenin-enhanced chemiluminescence. Hcy-induced expression of p38MAPK protein was measured by Western blotting analysis.Atorvastatin inhibited endothelial cell apoptosis induced by 1 mmol/L Hcy in a dose-dependent manner and the maximal inhibitory effect was reached at 100 micromol/L. Atorvastatin (10 micromol/L) significantly suppressed Hcy (1 mmol/L for 30 min) induced ROS accumulation (3.17+/-0.33 vs 4.34+/-0.31, P<0.05). Atorvastatin (10 micromol/L) also antagonized Hcy (1 mmol/L for 30 min) induced activation of NADPH oxidase (2.57+/-0.49 vs 3.33+/-0.6, P<0.05). Furthermore, atorvastatin inhibited Hcy-induced phosphorylation of p38 MAPK (1.7+/-0.1 vs 2.22+/-0.25, P<0.05), similar effects occurred with DPI, NAC and SB203580.Atorvastatin may inhibit Hcy-induced ROS accumulation and endothelium cell apoptosis through an NADPH oxidase and/or p38MAPK-dependent mechanisms, all of which may contribute to atorvastatin-induced beneficial effect on endothelial function." @default.
- W2070177458 created "2016-06-24" @default.
- W2070177458 creator A5023713562 @default.
- W2070177458 creator A5024596008 @default.
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- W2070177458 date "2009-09-21" @default.
- W2070177458 modified "2023-10-17" @default.
- W2070177458 title "Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling" @default.
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- W2070177458 doi "https://doi.org/10.1038/aps.2009.135" @default.
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