Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway.
This study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway.
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Xiantao
X
Wang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Yuhan
Y
Sun
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Huafeng
H
Yang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Yuanxi
Y
Lu
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Lang
L
Li
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002478:Cells, Cultured; D008077:Lipoproteins, LDL / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D008077:Lipoproteins, LDL; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein