Abstract |
The main purpose of this study is to evaluate the effect of echinacoside (ECH) on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanism. PASMCs were incubated under normoxia (nor), hypoxia (hyp), hypoxia + 0.35 mM ECH (hyp + ECH0.35), or hypoxia + 0.4 mM ECH (hyp + ECH0.4) for 24 h. Cell viability was assessed by MTS assays. The morphology of apoptosis was observed by DAPI staining, and apoptosis was quantified by flow cytometric analysis. Caspase-3 activity was determined by immunohistochemistry and real-time PCR, and the expressions of HIF-1α, Bax, Bcl-2, and Fas were determined by real-time PCR. Hypoxia induced significant proliferation of PASMCs, which could be inhibited by ECH in a concentration-dependent manner. This was associated with apoptosis of PASMCs. Z-DEVD-FMK could partly reduce the suppression effect of ECH; protein and gene expression of caspase-3 were significantly higher in the hyp + ECH0.4 and hyp + ECH0.35 groups. ECH significantly increased the expressions of Bax and Fas, but decreased the expressions of Bcl-2 and HIF-1α. ECH could inhibit hypoxia-induced proliferation of rat PASMCs, which is associated with apoptosis of PASMCs and improvement of hypoxia. ECH might be a potential agent for prevention and treatment of hypoxia-induced PAH.
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Authors | Xiang-Yun Gai, Feng Tang, Jing Ma, Ke-Wu Zeng, Sheng-Lan Wang, Ya-Ping Wang, Ta-Na Wuren, Dian-Xiang Lu, Yi Zhou, Ri-Li Ge |
Journal | Journal of pharmacological sciences
(J Pharmacol Sci)
Vol. 126
Issue 2
Pg. 155-63
( 2014)
ISSN: 1347-8648 [Electronic] Japan |
PMID | 25341567
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bax protein, rat
- Fas protein, rat
- Glycosides
- Hif1a protein, rat
- Hypoxia-Inducible Factor 1, alpha Subunit
- Proto-Oncogene Proteins c-bcl-2
- bcl-2-Associated X Protein
- fas Receptor
- Caspase 3
- echinacoside
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Topics |
- Animals
- Apoptosis
(drug effects)
- Caspase 3
(genetics, metabolism)
- Cell Hypoxia
(physiology)
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Depression, Chemical
- Dose-Response Relationship, Drug
- Gene Expression
(drug effects)
- Glycosides
(pharmacology)
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Male
- Muscle, Smooth, Vascular
(cytology, enzymology)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Pulmonary Artery
(cytology, enzymology)
- Rats, Wistar
- Vascular Remodeling
(drug effects)
- bcl-2-Associated X Protein
(genetics, metabolism)
- fas Receptor
(metabolism)
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