Electronegative LDL induction of apoptosis in macrophages: involvement of Nrf2
| Autor: | L. A. Faine, D.M. Grosso, B. de las Heras, A.M.C. Pedrosa, Dulcinéia Saes Parra Abdalla, Lisardo Boscá |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD36 Antigens
Programmed cell death Fas Ligand Protein NF-E2-Related Factor 2 CD36 Blotting Western Fluorescent Antibody Technique Apoptosis Fas ligand Mice Animals Humans RNA Messenger Molecular Biology Caspase Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Mice Knockout Reactive oxygen species biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Cell Biology Fas receptor Molecular biology Cell biology Lipoproteins LDL Mice Inbred C57BL chemistry biology.protein Macrophages Peritoneal lipids (amino acids peptides and proteins) Tumor necrosis factor alpha Female Reactive Oxygen Species Biomarkers |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0006-3002 |
| Popis: | The aim of this study was to determine the apoptotic pathways and mechanisms involved in electronegative LDL [LDL(-)]-induced apoptosis in RAW 264.7 macrophages and the role of Nrf2 in this process. Incubation of RAW 264.7 macrophages with LDL(-) for 24 h resulted in dose-dependent cell death. Activated caspases were shown to be involved in the apoptosis induced by LDL(-); incubation with the broad caspase inhibitor z-VAD prevented apoptosis in LDL(-)-treated cells. CD95 (Fas), CD95 ligand (FasL), CD36 and the tumor necrosis factor (TNF) ligand Tnfsf10 were overexpressed in LDL(-)-treated cells. However, Bax, Bcl-2 and Mcl-1 protein levels remained unchanged after LDL(-) treatment. LDL(-) promoted hyperpolarization of the mitochondrial membrane, elevated reactive oxygen species (ROS) production and translocation of Nrf2 to the nucleus, a process absent in cells treated with native LDL. Elicited peritoneal macrophages from Nrf2-deficient mice exhibited an elevated apoptotic response after challenge with LDL(-), together with an increase in the production of ROS in the absence of alterations in CD36 expression. These results provide evidence that CD36 expression induced by LDL(-) is Nrf2-dependent. Also, it was demonstrated that Nrf2 acts as a compensatory mechanism of LDL(-)-induced apoptosis in macrophages. © 2009 Elsevier B.V. All rights reserved. This study was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and by BFU2008-02161 from MICINN. |
| Databáze: | OpenAIRE |
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