Astragaloside IV protects against C/EBP homologous protein-mediated apoptosis in oxidized low-density lipoprotein-treated macrophages by promoting autophagy. 2022

Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China; Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China. Electronic address: xueyu2006823@126.com.

Astragaloside Ⅳ (AS-Ⅳ) is one of the main active components extracted from Astragalus membranaceus that exerts an antiatherosclerotic effect. Our study explored the underlying anti-apoptotic effects and the mechanisms of action of AS-Ⅳ in oxidized low-density lipoprotein (oxLDL)-stimulated macrophages and in vulnerable plaques. The results showed that AS-Ⅳ lowered the oxLDL-induced lipid content and reversed the oxLDL-induced reduction in cell viability and elevation in lactate dehydrogenase (LDH) leakage and apoptosis in RAW264.7 macrophages, similar to the effects of 4-phenylbutyric acid (PBA, an ER stress inhibitor). In addition, consistent with the effect exerted by PBA, AS-Ⅳ inhibited oxLDL-triggered ER stress activation by decreasing the level of inositol-requiring enzyme1 phosphorylation and transcription factor 6 nuclear translocation and upregulating the protein and mRNA expression of glucose-regulated protein 78 (GPR78) and C/EBP homologous protein (CHOP). As expected, autophagy activation was induced by AS-IV, evidenced by increased expression of microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ), autophagy-related gene 5, and beclin-1 in macrophages. Furthermore, after pretreatment with 3-methyladenine and beclin-1 small interfering RNA, the inhibitory role played by AS-Ⅳ in oxLDL-induced ER stress-CHOP-mediated macrophage apoptosis was weakened, while its inhibitory effect was further enhanced by rapamycin pretreatment. Moreover, administration of AS-Ⅳ or rapamycin to Apoe-/- mice upregulated LC3-Ⅱ expression and collagen content but decreased CHOP expression, macrophage apoptosis, and lipid areas. Overall, by promoting autophagy, AS-Ⅳ effectively protects macrophages from oxLDL-induced apoptosis mediated by ER stress-CHOP, which may reinforce the stability of atherosclerotic plaques.

UI MeSH Term Description Entries
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D000071186 Beclin-1 An autophagy related protein which functions as a core subunit of PHOSPHATIDYLINOSITOL 3-KINASE MULTIPROTEIN COMPLEXES. It mediates the formation of phosphatidylinositol 3-phosphate and functions in AUTOPHAGY, where it is required for maturation of the AUTOPHAGOSOME. It also functions in ENDOCYTOSIS and CYTOKINESIS as part of a separate complex. Beclin-1 associates with INTRACELLULAR MEMBRANES and interacts with the PROTO-ONCOGENE PROTEINS C-BCL-2 and BCL-X PROTEIN. ATG-6 Protein,ATG6 Protein,Beclin-1 Protein,Beclin1,Coiled-coil Myosin-like Bcl2-interacting Protein,GT197 Protein,ATG 6 Protein,Beclin 1,Beclin 1 Protein,Coiled coil Myosin like Bcl2 interacting Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D012503 Saponins A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycone moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Saponin
D014315 Triterpenes A class of terpenes (the general formula C30H48) formed by the condensation of six isoprene units, equivalent to three terpene units. Triterpene,Triterpenoid,Triterpenoids
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
July 2012, Experimental biology and medicine (Maywood, N.J.),
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
December 2016, Placenta,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
September 2007, Proceedings of the National Academy of Sciences of the United States of America,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
April 2008, Journal of lipid research,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
March 2019, Medical science monitor : international medical journal of experimental and clinical research,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
October 2016, Molecular medicine reports,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
April 2015, DNA and cell biology,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
September 2017, Molecular medicine reports,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
August 2011, DNA repair,
Hua Tian, and Tong Wang, and Yumei Zhang, and Tianqi Pan, and Shutong Yao, and Huayun Yu, and Ke Ma, and Shijun Wang
October 2018, Circulation,
Copied contents to your clipboard!