Regulation of the induction of ornithine decarboxylase in keratinocytes by retinoids
| Autor: | Janet H. Prystowsky, Zai S. Zheng, G Z Xue |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Keratinocytes
medicine.medical_specialty genetic structures Ultraviolet Rays Retinoic acid Etretinate Biology Ornithine Decarboxylase Biochemistry Gene Expression Regulation Enzymologic Acitretin Ornithine decarboxylase Cell Line chemistry.chemical_compound Retinoids Epidermal growth factor Internal medicine medicine Humans Molecular Biology Glyceraldehyde 3-phosphate dehydrogenase Regulation of gene expression Epidermal Growth Factor Cell Biology ErbB Receptors Endocrinology chemistry Enzyme Induction biology.protein Signal transduction hormones hormone substitutes and hormone antagonists medicine.drug Research Article Protein Binding |
| Popis: | Treatment of SV40-transformed keratinocytes (Z114) with epidermal growth factor (EGF) resulted in an increase in ornithine decarboxylase (ODC) activity and a dose-dependent increase in ODC mRNA levels. Pretreatment of keratinocytes with all-trans-retinoic retinoic acid inhibited the EGF induction of ODC activity. In both quiescent and EGF-stimulated cells, all-trans-retinoic acid inhibited ODC gene transcription and lowered ODC mRNA levels, whereas glyceraldehyde phosphate dehydrogenase expression remained unaffected. Treatment with all-trans-retinoic acid for 24 h resulted in a dose- and time-dependent decrease of up to 52% in EGF binding to EGF receptors and a 30-75% decrease in EGF-receptor quantity. In addition, when cells were treated with both UV radiation and all-trans-retinoic acid, their effects were additive in causing a decrease in EGF binding. Blocking of EGF receptors with a neutralizing antibody for EGF receptors inhibited the induction of ODC activity by EGF. The effects of several other retinoids, including Ro15-0778, etretinate, Ro13-7410, etarotene, Ro40-8757, 13-cis-retinoic acid and acitretin, were also studied to determine their effects on EGF binding and ODC activity. Two of these other retinoids, 13-cis-retinoic acid and Ro13-7410, inhibited EGF binding the most (35-46%, P < 0.001); several others (etarotene, Ro40-8757 and etretinate) were less effective (7-16%), but significantly decreased EGF binding (P < 0.05), and two retinoids (Ro15-0778 and acitretin) showed no significant effect on EGF binding. In contrast, all of the retinoids tested inhibited the induction of ODC activity by EGF, although etretinate and Ro15-0778 were less effective. EGF signal transduction is important in ODC gene regulation, and retinoids are significant modulators of this pathway. |
| Databáze: | OpenAIRE |
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