Caihong Liang1,2, Xiaochen Wang3, Jianping Hu4, Xiaoqing Lian2, Tiantian Zhu2, Hui Zhang4, Ning Gu1,5, Jun Li4. 1. Nanjing University of Chinese Medicine, Nanjing, China. 2. Department of cardiovascular, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China. 3. Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Department of Liver surgery, Collaborative Innovation Center for Cancer Personalized Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 4. Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China. 5. Department of cardiovascular, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Abstract
BACKGROUND/AIMS: Critical roles of phosphatase receptor type O (PTPRO) and toll-like receptor 4 (TLR4) have been implicated in inflammation. However, little is known about their functional effects on atherosclerosis (AS). We aim to study their potential function in AS. METHODS: An oxidized low-density lipoprotein (ox-LDL) induced AS model constructed with PTPRO over-expressing RAW264.7 cells and PTPRO knockout macrophages. Cell apoptosis was assayed by flow cytometry and fatty accumulation was evaluated by oil red staining. The production of ROS (reactive oxygen species), SOD (superoxide dismutase), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) was evaluated. Western blot was performed to detect the expression of CD36, TLR4 and nuclear factor kB (NF-κB). RESULTS: PTPRO expression was promoted in a dose-dependent and time-dependent manner following ox-LDL challenging. In PTPRO-over-expressing cells, CD36 expression and the level of oil-red staining, TC and TG were increased; ROS production, MDA and level of cell apoptosis were improved, but SOD was reduced. However, in PTPRO knockout cells opposite results were found. TLR4 and NF-κB/p65 phosphorylation was significantly enhanced in PTPRO over-expressing cells, while significantly down-regulated in PTPRO knockout cells. CONCLUSION: PTPRO plays ital roles in AS via promoting ox-LDL induced oxidative stress and cell apoptosis through TLR4/NF-κB pathway.
BACKGROUND/AIMS: Critical roles of phosphatase receptor type O (PTPRO) and toll-like receptor 4 (TLR4) have been implicated in inflammation. However, little is known about their functional effects on atherosclerosis (AS). We aim to study their potential function in AS. METHODS: An oxidized low-density lipoprotein (ox-LDL) induced AS model constructed with PTPRO over-expressing RAW264.7 cells and PTPRO knockout macrophages. Cell apoptosis was assayed by flow cytometry and fatty accumulation was evaluated by oil red staining. The production of ROS (reactive oxygen species), SOD (superoxide dismutase), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) was evaluated. Western blot was performed to detect the expression of CD36, TLR4 and nuclear factor kB (NF-κB). RESULTS:PTPRO expression was promoted in a dose-dependent and time-dependent manner following ox-LDL challenging. In PTPRO-over-expressing cells, CD36 expression and the level of oil-red staining, TC and TG were increased; ROS production, MDA and level of cell apoptosis were improved, but SOD was reduced. However, in PTPRO knockout cells opposite results were found. TLR4 and NF-κB/p65 phosphorylation was significantly enhanced in PTPRO over-expressing cells, while significantly down-regulated in PTPRO knockout cells. CONCLUSION:PTPRO plays ital roles in AS via promoting ox-LDL induced oxidative stress and cell apoptosis through TLR4/NF-κB pathway.
Authors: Michael Rode; Kolja Nenoff; Kerstin Wirkner; Katrin Horn; Andrej Teren; Ralf Regenthal; Markus Loeffler; Joachim Thiery; Achim Aigner; Janne Pott; Holger Kirsten; Markus Scholz Journal: PLoS One Date: 2022-04-21 Impact factor: 3.240
Authors: Anca Liliana Cismaru; Deborah Rudin; Luisa Ibañez; Evangelia Liakoni; Nicolas Bonadies; Reinhold Kreutz; Alfonso Carvajal; Maria Isabel Lucena; Javier Martin; Esther Sancho Ponce; Mariam Molokhia; Niclas Eriksson; Stephan Krähenbühl; Carlo R Largiadèr; Manuel Haschke; Pär Hallberg; Mia Wadelius; Ursula Amstutz Journal: Genes (Basel) Date: 2020-10-29 Impact factor: 4.096