Depletion of CPEB1 protects against oxidized LDL-induced endothelial apoptosis and inflammation though SIRT1/LOX-1 signalling pathway. 2019

Kaicheng Xu, and Xiwen Liu, and Guanghao Ren, and Dexin Yin, and Suli Guo, and Yue Zhao
Department of Anesthesiology, China-Japan Union Hospital JiLin University, Chang Chun, JiLin, 130033, China.

Atherosclerosis (AS) is a chronic inflammatory disease that results from Oxidized low-density lipoprotein (Ox-LDL) induced endothelial dysfunction. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is closely related to the development of epithelial cells, but the role of CPEB1 in AS remains unknown. The RNA and protein levels of CPEB1 expression are increased by Ox-LDL exposure, which is abrogated by c-Jun amino-terminal kinase (JNK) inhibitor SP600125. CPEB1 small interfering RNA (siRNA) suppressed the oxidative stress, inflammation, and apoptosis. Furthermore, CPEB1 siRNA enhanced the sirtuin 1 (SIRT1) transcription levels in Ox-LDL-treated HUVECs. Co-Immunoprecipitation (Co-IP) assay showed that CPEB1 siRNA declined the ubiquitination of SIRT1, and SIRT1 siRNA enhanced the Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which were decreased by CPEB1 siRNA. In addition, LOX-1 and SIRT1 attenuated the protection of SIRT1 siRNA on Ox-LDL-induced oxidative stress. Therefore, our study revealed that CPEB1 depletion might play an anti-inflammatory and antiapoptotic role in Ox-LDL-induced apoptosis and inflammation though SIRT1/LOX-1 signalling pathway.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
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
D004727 Endothelium A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body. Endotheliums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
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
D050197 Atherosclerosis A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA. Atherogenesis,Atherogeneses,Atheroscleroses
D051127 Scavenger Receptors, Class E A class of oxidized LDL receptors that contain C-type lectin-like extracellular domains. Scavenger Receptors, Class E, Type I,Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1,OLR1 Protein,Oxidized Low-Density Lipoprotein Receptor 1,SR-E Proteins,SR-EI Proteins,Lectin Like Oxidized Low Density Lipoprotein Receptor 1,Oxidized Low Density Lipoprotein Receptor 1,SR EI Proteins
D056564 Sirtuin 1 A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation. Silent Mating Type Information Regulation 2 Homolog 1,Sirt1

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