High-Density Lipoprotein Prevents Endoplasmic Reticulum Stress-Induced Downregulation of Liver LOX-1 Expression.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a specific cell-surface receptor for oxidized-low-density lipoprotein (ox-LDL). The impact of high-density lipoprotein (HDL) on endoplasmic reticulum (ER) stress-mediated alteration of the LOX-1 level in hepatocytes remains unclear. We aimed to investigate the impact on LOX-1 expression by tunicamycin (TM)-induced ER stress and to determine the effect of HDL on TM-affected LOX-1 expression in hepatic L02 cells. Overexpression or silencing of related cellular genes was conducted in TM-treated cells. mRNA expression was evaluated using real-time polymerase chain reaction (PCR). Protein expression was analyzed by western blot and immunocytochemistry. Lipid uptake was examined by DiI-ox-LDL, followed by flow cytometric analysis. The results showed that TM induced the upregulation of ER chaperone GRP78, downregulation of LOX-1 expression, and lipid uptake. Knock down of IRE1 or XBP-1 effectively restored LOX-1 expression and improved lipid uptake in TM-treated cells. HDL treatment prevented the negative impact on LOX-1 expression and lipid uptake induced by TM. Additionally, 1-10 μg/mL HDL significantly reduced the GRP78, IRE1, and XBP-1 expression levels in TM-treated cells. Our findings reveal that HDL could prevent the TM-induced reduction of LOX-1 expression via inhibiting the IRE1/XBP-1 pathway, suggesting a new mechanism for beneficial roles of HDL in improving lipid metabolism.
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Dan
D
Hong
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ling-Fang
LF
Li
Department of Cardiovascular Medicine, The Affiliated Hospital of Chengde Medical College, Hebei, China.
Hai-Chao
HC
Gao
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiang
X
Wang
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Chuan-Chang
CC
Li
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ying
Y
Luo
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yong-Ping
YP
Bai
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Guo-Gang
GG
Zhang
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071701:Regulatory Factor X Transcription Factors; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D051127:Scavenger Receptors, Class E; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C099252:oxidized low density lipoprotein; D014415:Tunicamycin; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases