Evidence for oxidative activation of c-Myc-dependent nuclear signaling in human coronary smooth muscle cells and in early lesions of Watanabe heritable hyperlipidemic rabbits: protective effects of vitamin E
| Autor: | Gianluigi Condorelli, Tammam Youssef, Flavia Franconi, Vittorio Anania, Claudio Napoli, SilviaAnna Ciafré, Wulf Palinski, Filomena de Nigris |
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| Přispěvatelé: | de NIGRIS, Filomena, Youssef, T, Ciafré, S, Franconi, F, Anania, V, Condorelli, G, Palinski, W, Napoli, Claudio |
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_treatment
Cell Basic helix-loop-helix leucine zipper transcription factors Cell Cycle Proteins Cardiorespiratory Medicine and Haematology coronary disease Muscle Smooth Vascular Pathogenesis Medicine Vitamin E Cells Cultured Cultured Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Settore BIO/13 Basic-Leucine Zipper Transcription Factors Proto-Oncogene Proteins c-myc Animals Carrier Proteins Hyperlipidemias Lipoproteins LDL Rabbits DNA-Binding Proteins Kruppel-Like Transcription Factors Humans Transcription Factor DP1 Retinoblastoma-Binding Protein 1 Signal Transduction Transcription Factors Oxidation-Reduction E2F Transcription Factors medicine.anatomical_structure antioxidants Public Health and Health Services Muscle lipids (amino acids peptides and proteins) Smooth Signal transduction Cardiology and Cardiovascular Medicine medicine.medical_specialty Cells Lipoproteins Clinical Sciences LDL Physiology (medical) Internal medicine Vascular E2F business.industry Activator (genetics) Endocrinology Cardiovascular System & Hematology Cell culture atherosclerosis business |
| Zdroj: | Circulation, vol 102, iss 17 Scopus-Elsevier |
| Popis: | Background —Oxidized LDL (oxLDL) promotes atherogenesis, and antioxidants reduce lesions in experimental models. OxLDL-mediated effects on c-Myc are poorly characterized, and those on c-Myc nuclear pathways are completely unknown. c-Myc stimulates smooth muscle cell (SMC) proliferation and could be involved in atherosclerosis. We investigated the early effects of oxLDL and α-tocopherol on c-Myc, its binding partner Max, and the carboxy-terminal domain–binding factors activator protein-2 and elongation 2 factor in human coronary SMCs. We also investigated whether 9-week treatment of Watanabe heritable hyperlipidemic (WHHL) rabbits with diet-enriched α-tocopherol reduces c-Myc expression and oxLDL in the left coronary artery. Methods and Results —OxLDL enhanced c-Myc/Max expression and transcription by cotransfection assay and the nuclear activities of E2F and activator protein-2 by binding shift and supershift in coronary SMCs. α-Tocopherol significantly reduced these molecular events. Furthermore, α-tocopherol reduced early lesions, SMC density, and the immunohistochemical presence of c-Myc, which colocalized with oxLDL/foam cells in the coronaries of WHHL rabbits. Conclusions —We provide the first evidence that oxLDL and α-tocopherol may influence c-Myc activation and several c-Myc–dependent signaling pathways in human coronary SMCs. The observation that in vivo, an antioxidant reduces both c-Myc and oxLDL in early coronary lesions of rabbits is consistent with, but does not prove, the hypothesis that c-Myc–dependent factors activated by oxidative processes contribute to atherogenesis and coronary heart disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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