An in vitro system for identifying agents capable of changing serum lipoprotein(a) concentration by regulating the transcriptional activity of the apolipoprotein(a) gene promoter
| Autor: | Shiro Saito, Kazumasa Miyamoto, Ayako Watanabe, Nobuaki Mima, Hiroyuki Azuma, Hiroshi Yamaguchi, Yasuhiko Kanagawa, Toshio Shigekiyo, Mitsuo Shirakawa |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Hepatoblastoma Male medicine.medical_specialty Apolipoprotein B Transcription Genetic Recombinant Fusion Proteins Biophysics Tretinoin Apoprotein(a) Transfection Biochemistry Cell Line Leukemia Promyelocytic Acute In vivo Genes Reporter Internal medicine medicine Tumor Cells Cultured Humans Vitamin E Luciferase Luciferases Promoter Regions Genetic Molecular Biology DNA Primers Regulation of gene expression Triiodothyronine biology Base Sequence Interleukin-6 Danazol Liver Neoplasms Promoter Cell Biology Lipoprotein(a) DNA Middle Aged Gene Expression Regulation Neoplastic Kinetics Endocrinology Apolipoproteins biology.protein Female Lipoprotein |
| Zdroj: | Biochemical and biophysical research communications. 227(2) |
| ISSN: | 0006-291X |
| Popis: | A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and independent risk factor for cardiovascular disease. We examined the effects of agents on the transcriptional activity of the apolipoprotein(a) [apo(a)] gene promoter and determined whether drugs identified by this assay would affect the serum concentration of Lp(a) in vivo. All-trans-retinoic acid (ATRA) and interleukin-6 increased the transcriptional activity of the apo(a) gene promoter 2.1- and 2.5-fold, respectively, whereas danazol reduced activity to 76% of the control value. Triiodothyronine had no effect on transcriptional activity. Treatment of two acute promyelocytic leukemia patients with ATRA induced maximal 2.7- and 3.2-fold increases in serum Lp(a) concentrations, respectively. Thus, the in vitro luciferase assay system is capable of identifying agents that affect the serum concentration of Lp(a) and thus may prove beneficial in the screening of new drugs for treatment of individuals with high serum Lp(a) concentrations. |
| Databáze: | OpenAIRE |
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