Endoplasmic reticulum stress is involved in acetylated low density lipoprotein-induced apoptosis in THP-1 differentiated macrophages / 中华肾脏病杂志

ABSTRACT

ObjectiveTo clarify why accelarated atheroslcerosis is complicated in chronic kidney disease patients, and to investigate whether endoplasmic reticuhm (ER) stress can be observed in acetylated low density lipepmtein (ACLDL)-induced apoptosis in THP-1 macrophages differentiated by 160 nmol/L PMA for five days. Methods Hoechst 33258 stain and caspase 3,7 assay were used to detect apeptosis. Oil red O was used to examine the lipid droplet. High performance liquid chromatography was used to measure intracelhlar free cholesterol (FC) and cholesterol ester (CE). Western blot was applied to demonstrate the protein level of acylcoenzyme A cholesterol acyltransferase(ACAT)1, growth arrest and DNA damage(CHOP) and Bcl-2. Real-time PCR was used to detect the changes of mRNAs. Results ACLDL could induce THP-1 macrophages apoptosis in time-and dose-dependent manner. After exposure to 100 mg/L ACLDL for 24 hours, the level of free cholesterol and cholesterol ester mass had a significant increment by 1.5-and 2.4-fold respectively (P＜0.01). CHOP increased and Bcl-2 decreased both in protein and mRNA levels. ACLDL loading also resulted in an increase of ACAT1 protein without any change in mRNA level. ConclusionIn THP-1 macrophages foam cell, apoptosis can be induced by ACLDL accompanied by ER stress pathway activation.