Regulation of HMG-CoA Synthase and HMG-CoA Reductase by Insulin and Epidermal Growth Factor in HaCaT Keratinocytes
| Autor: | Angela M. Farrell, Ian R. Harris, Wilfried Siefken, Klaus-Peter Wittern, Hendrik Höppner |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Hydroxymethylglutaryl-CoA Synthase
Keratinocytes medicine.medical_treatment Coenzyme A Dermatology Reductase Biochemistry Cell Line chemistry.chemical_compound Epidermal growth factor medicine Humans Insulin RNA Messenger Promoter Regions Genetic Molecular Biology Calcimycin Binding Sites Epidermal Growth Factor Ionophores integumentary system biology Growth factor Cell Biology Transcription Factor AP-1 medicine.anatomical_structure chemistry HMG-CoA reductase biology.protein Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Mevalonate pathway Keratinocyte |
| Zdroj: | Journal of Investigative Dermatology. 114(1):83-87 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2000.00822.x |
| Popis: | Synthesis of cholesterol, via the isoprenoid/mevalonate pathway, is required for keratinocyte growth and differentiation, and maintenance of the stratum corneum lipid lamellae. 3-hydroxy-3-methylglutaryl coenzyme A synthase catalyzes the first step in isoprenoid/mevalonate synthesis and under some conditions controls the flux into the pathway. We have investigated whether selected growth factors and hormones could increase 3-hydroxy-3-methylglutaryl coenzyme A synthase mRNA in keratinocytes. Northern blotting was used to demonstrate that 10 microg per ml insulin and 0.1 microg per ml epidermal growth factor both increased steady-state levels of 3-hydroxy-3-methylglutaryl coenzyme A synthase mRNA by 2.5 and 6-fold, respectively. Epidermal growth factor and insulin also increased 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme activity. 3-hydroxy-3-methylglutaryl coenzyme A synthase promoter activity in a luciferase reporter construct was increased 2-fold by insulin and 2.9-fold by epidermal growth factor. When a mutation in the sterol regulatory element was introduced into the 3-hydroxy-3-methylglutaryl coenzyme A synthase promoter, activity was not increased by insulin, but was increased by epidermal growth factor. Mutation of an AP-1 site in the 3-hydroxy-3-methylglutaryl coenzyme A synthase promoter did not affect the increase in activity following treatment with insulin or epidermal growth factor. Therefore, 3-hydroxy-3-methylglutaryl coenzyme A synthase expression in keratinocytes is regulated by insulin and epidermal growth factor by different mechanisms. These results suggest a role for hormones and growth factors in the control of epidermal cholesterol synthesis. |
| Databáze: | OpenAIRE |
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