7-Ketocholesterol induces ATM/ATR, Chk1/Chk2, PI3K/Akt signalings, cytotoxicity and IL-8 production in endothelial cells

摘要: // Mei-Chi Chang 1,2 , Yi-Jane Chen 3,* Eric Jein-Wein Liou 2 Wan-Yu Tseng 3 Chiu-Po Chan Hseuh-Jen Lin 4 Wan-Chuen Liao Ya-Ching 5 Po-Yuan Jeng and Jiiang-Huei 1 Biomedical Science Team, Gung University of Technology, Kwei-Shan, Taoyuan, Taiwan Department Dentistry, Memorial Hospital, Taipei, School Dentistry National Medical College Hospital Show Chwan Changhua, Mackey * This author have contributes equally to the first Correspondence to: Jeng, email: Chan, Keywords : apoptosis, atherosclerosis, cytotoxicity, endothelial cells, inflammation,Gerotarget Received September 13, 2016 Accepted October 06, Published 11, Abstract Cardiovascular diseases (atherosclerosis, stroke, myocardiac infarction etc.) are major systemic elder peoples in world. is possibly due increased levels oxidized low-density lipoproteins (oxLDLs) such as 7-ketocholesterol (7-KC) lysophosphatidylcholine (LPC) that damage vascular induce inflammatory responses, elevate risk cardiovascular diseases, Alzheimer’s disease, age-related macular degeneration. However toxic effects 7-KC on cells not known. In this study, showed cytotoxicity at concentrations higher than 10 µg/ml. stimulated ATM/Chk2, ATR-Chk1 p53 signaling pathways cells. also induced G0/G1 cell cycle arrest apoptosis with an inhibition Cyclin dependent kinase (Cdk1) cyclin B1 expression. Secretion expression IL-8 were by 7-KC. further intracellular ROS production shown increase DCF fluorescence Akt phosphorylation. LY294002 attenuated 7-KC-induced mRNA These results indicate oxLDLs may contribute pathogenesis thrombosis induction damage, responses. events associated production, activation ATR/Chk1, PI3K/Akt pathways.