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Cytotoxicity effects of tert‐butyl hydroperoxide‐induced p53 ‐ mediated cell‐cycle arrest, apoptosis and aging in rat aortic endotheial cells and aorta: inhibition by Angelica sinesis extracts
Author(s) -
Yeh YuehChiao,
Liu TsunJui,
Shin TzuHui,
Wang LiChuan,
Lai HuiChin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.651.6
Subject(s) - apoptosis , telomerase , cell cycle checkpoint , pharmacology , cell cycle , senescence , oxidative stress , dna damage , programmed cell death , inflammation , chemistry , microbiology and biotechnology , biology , immunology , biochemistry , dna , gene
Endotheial dysfunction is one of the underlying causes for vascular diseases. tert‐butyl hydroperoxide (t‐BHP), a short‐chain lipid hydroperoxide analog, has been referred to cause cellular senescence in different systems. This study aims to investigate whether the potent antioxidant Angelica sinesis (AS) extracts, often used in traditional Chinese medicine, could protect against the t‐BHP induced toxicity in rat aortic endothelium. Primary cultured endothelial cells (ECs) were treated with vehicle or t‐BHP. Exposure of ECs to lower doses t‐BHP caused cellular senescence and apoptosis, and higher doses initiated cell‐cycle arrest, telomerase acitivty diminished, and cellular inflammation. However, these adverse effects could be antagonized by AS extracts pretreatment via p53‐dependent mitochondrial signaling pathways. In terms of in vivo study, male rats at 6‐or 24‐week of age were administrated with vehicle or t‐BHP. Significanty increased TUNEL‐ and SA‐beta‐gal‐positive cells, provoked caspase‐3 activities, and inhibition of telomerase activities in aorta from t‐BHP‐treated groups. These results suggest t‐BHP impaired vascular cell survival at least partially by activating the p53‐mediated signaling pathway and AS can counteract these actions of t‐BHP to protect the aortic endotheium from t‐BHP induced dysfunction.(Supported by research grants from NSC992313B343001‐MY3, Taiwan)