Inhibition of migration and proliferation of vascular smooth muscle cells by dehydroepiandrosterone sulfate
| Autor: | Ryousuke Fukui, Nakaaki Ohsawa, Masahiro Amakawa, Daisuke Furutama |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Aging
endocrine system medicine.medical_specialty Vascular smooth muscle Arteriosclerosis medicine.drug_class Dehydroepiandrosterone Muscle Smooth Vascular Androgen chemistry.chemical_compound Dehydroepiandrosterone sulfate Cell Movement Internal medicine polycyclic compounds medicine Animals skin and connective tissue diseases Receptor Steroid Molecular Biology Cells Cultured biology Dehydroepiandrosterone Sulfate Atherosclerosis Estrogen Dissociation constant Fibronectin Endocrinology chemistry Cell culture biology.protein Molecular Medicine Rabbits human activities Cell Division hormones hormone substitutes and hormone antagonists |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1406:107-114 |
| ISSN: | 0925-4439 |
| Popis: | Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are the most abundant steroids in humans, and their serum concentrations progressively decrease with age. Although relationships between DHEA(-S) and many age-related illnesses have been postulated, the mechanisms for their effects remain unknown, and specific receptors for these molecules have not been identified. In this paper, to investigate the role of DHEA(-S) in atherogenesis, we studied the proliferation and migration of a rabbit vascular smooth muscle cell line, SM-3, in the presence of DHEA(-S). Cellular proliferation was inhibited by DHEA-S, and to a lesser extent by DHEA. Modified Boyden's chamber assays revealed that DHEA-S inhibited the migration of SM-3 cells toward PDGF-BB. In cell attachment assays, DHEA-S inhibited the attachment of SM3 cells to fibronectin. It was suggested that the inhibitory effect of DHEA-S for SM-3 proliferation and migration was due to the decreased interaction with fibronectin. Scatchard analysis revealed the presence of two populations of DHEA-S binding sites in the nuclear fraction, and a smaller number in the cytosolic fraction. Since the dissociation constant of the higher affinity site was similar to the serum DHEA-S concentration in humans (Kd=5.8μM), this binding site could be functional under physiologic conditions. These findings suggest that there may be receptor-mediated anti-atherogenic actions of DHEA-S. |
| Databáze: | OpenAIRE |
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