Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and ApoAI-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in intron 1
| Autor: | Michael R. Hayden, Nagat Bissada, Bing Tan, Angela Brooks-Wilson, Bart Staels, Blair R. Leavitt, Guoqing Liu, Sherrie Tafuri, Roshni R. Singaraja, Susanne M. Clee, Virginie Bocher, Cheryl L. Wellington, Catherine Fievet, Yu-Zhou Yang, Anita Kwok, Lin-Hua Zhang, Erick R. James |
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| Rok vydání: | 2001 |
| Předmět: |
Receptors
Retinoic Acid Receptors Cytoplasmic and Nuclear Biochemistry chemistry.chemical_compound Mice High-density lipoprotein Tumor Cells Cultured Cloning Molecular Promoter Regions Genetic Cells Cultured Liver X Receptors Receptors Thyroid Hormone biology Reverse Transcriptase Polymerase Chain Reaction Orphan Nuclear Receptors Immunohistochemistry Lipids DNA-Binding Proteins Cholesterol Liver COS Cells lipids (amino acids peptides and proteins) Efflux ATP Binding Cassette Transporter 1 Transcriptional Activation Molecular Sequence Data Mice Transgenic Response Elements Transfection Cell Line In vivo Distribution (pharmacology) Animals Humans RNA Messenger Liver X receptor Molecular Biology Apolipoprotein A-I Base Sequence Models Genetic Macrophages Cholesterol HDL Intron Cell Biology Molecular biology Introns chemistry ABCA1 biology.protein ATP-Binding Cassette Transporters |
| Zdroj: | The Journal of biological chemistry. 276(36) |
| ISSN: | 0021-9258 |
| Popis: | By using BAC transgenic mice, we have shown that increased human ABCA1 protein expression results in a significant increase in cholesterol efflux in different tissues and marked elevation in high density lipoprotein (HDL)-cholesterol levels associated with increases in apoAI and apoAII. Three novel ABCA1 transcripts containing three different transcription initiation sites that utilize sequences in intron 1 have been identified. In BAC transgenic mice there is an increased expression of ABCA1 protein, but the distribution of the ABCA1 product in different cells remains similar to wild type mice. An internal promoter in human intron 1 containing liver X response elements is functional in vivo and directly contributes to regulation of the human ABCA1 gene in multiple tissues and to raised HDL cholesterol, apoAI, and apoAII levels. A highly significant relationship between raised protein levels, increased efflux, and level of HDL elevation is evident. These data provide proof of the principle that increased human ABCA1 efflux activity is associated with an increase in HDL levels in vivo. |
| Databáze: | OpenAIRE |
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