Protective effects of paeoniflorin against cobalt chloride-induced apoptosis of endothelial cells via HIF-1α pathway.

Abstract

Accumulating evidence has suggested the importance of hypoxia in the initiation and development of atherosclerotic lesion, and hypoxia has a profound impact on endothelial cell properties during cardiovascular disease processes. Paeoniflorin, isolated from the root of Paeonia lactiflora pall, can protect endothelial cells from hypoxic damage in a variety of ways, such as by enhancing the production of nitric oxide (NO) and decreasing the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This study evaluated the protective effects of paeoniflorin against cobalt chloride (CoCl2, a hypoxia-mimicking agent)-induced apoptosis of endothelial cells (CRL-1730) and the underlying mechanisms in vitro. Endothelial cells were exposed to CoCl2 with or without pre-treatment with different concentrations of paeoniflorin. After treated with 0.6mM CoCl2 for 24 h, endothelial cells showed significant decrease in cell viability and increased apoptosis rate, which could be reversed by pre-treatment with paeoniflorin. Similarly, pre-treatment with paeoniflorin could prevent CoCl2-induced hypoxia-induced factor-1α (HIF-1α) accumulation and down-regulate the expressions of p53 and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3). These findings indicate that paeoniflorin had effective protection against hypoxia-induced apoptosis of endothelial cells and that HIF-1α, p53 and BNIP3 might be involved in this process.

• Authors: Qiaoli Ji, Lina Yang, Jun Zhou, Rong Lin, Jiye Zhang, Qinqin Lin, Weirong Wang, Kaifan Zhang
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 26 Issue 3 Pg. 455-61 (Apr 2012) ISSN: 1879-3177 [Electronic] England
• PMID: 22269387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• BNIP3 protein, human
• Benzoates
• Bridged-Ring Compounds
• Glucosides
• Hypoxia-Inducible Factor 1, alpha Subunit
• Membrane Proteins
• Monoterpenes
• Proto-Oncogene Proteins
• Tumor Suppressor Protein p53
• peoniflorin
• Nitric Oxide
• Cobalt
• cobaltous chloride

Topics

• Apoptosis (drug effects)
• Benzoates (administration & dosage, isolation & purification, pharmacology)
• Bridged-Ring Compounds (administration & dosage, isolation & purification, pharmacology)
• Cell Hypoxia (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cobalt (toxicity)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Glucosides (administration & dosage, isolation & purification, pharmacology)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Monoterpenes
• Nitric Oxide (metabolism)
• Paeonia (chemistry)
• Plant Roots
• Proto-Oncogene Proteins (genetics, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)