Ginsenoside Rb1 inhibits vascular calcification as a selective androgen receptor modulator
| Autor: | Tsuyoshi Hashizume, Sumito Ogawa, Yusuke Asari, Ken-ichi Takayama, Aya Komuro, Masahiro Akishita, Michiko Nanao-Hamai, Bo-Kyung Son |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Transcriptional Activation 0301 basic medicine medicine.medical_specialty Ginsenosides Bicalutamide medicine.drug_class Estrogen receptor Apoptosis Young Adult 03 medical and health sciences Transactivation 0302 clinical medicine Cell Line Tumor Internal medicine medicine Humans Vascular Calcification Transrepression Pharmacology Chemistry PHTPP Prostate-Specific Antigen Androgen medicine.disease eye diseases 030104 developmental biology Endocrinology Selective androgen receptor modulator Receptors Androgen Intercellular Signaling Peptides and Proteins Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery medicine.drug Calcification |
| Zdroj: | European Journal of Pharmacology. 859:172546 |
| ISSN: | 0014-2999 |
| Popis: | Ginsenoside Rb1 (Rb1), a major component of ginseng, has a steroidal chemical structure, implying that it exerts sex hormone-like actions. Recent studies have been suggested cardioprotective actions of Rb1. However, the actions of Rb1 in vascular calcification, one of the significant pathological features associated with aging and atherosclerosis, have not been examined. In the present study, we examined the effects of Rb1 on vascular calcification, focusing on its androgen-like actions. Using inorganic phosphate (Pi)-induced calcification of vascular smooth muscle cells (VSMC), we found that Rb1, like testosterone, significantly inhibited calcium deposition in a concentration-dependent manner. Further, this inhibition of Rb1 was abolished by bicalutamide, an androgen receptor antagonist, but not by MPP or PHTPP, estrogen receptor α or β antagonists. Rb1 significantly inhibited apoptosis, one of the regulatory mechanisms of calcification, and restored growth arrest-specific gene 6 (Gas6) expression that was suppressed by Pi. Moreover, Rb1 transactivated Gas6, and proximal androgen-responsive element (ARE) of the promoter region was found to be crucial for Gas6 transactivation. In contrast, in a human prostate cancer cell line, testosterone-induced ARE activity was abrogated by Rb1. This antagonistic effect was also confirmed by the transrepression and downregulation of prostate-specific antigen in the presence of testosterone and Rb1 together. Thus, these findings provide a novel mechanistic insight into the vasculoprotective actions of Rb1 as a selective androgen receptor modulator, i.e., inhibitory effects on VSMC calcification through androgen receptor-mediated Gas6 transactivation and antagonistic effects in prostate cancer cells. |
| Databáze: | OpenAIRE |
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