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Underlying mechanisms of tert‐butyl hydroperoxide induced vascular cell dysfunction and senescence in rats: in vivo and in vitro studies
Author(s) -
Yeh Yueh-Chiao,
Liu Tsun-Jui,
Lo Jun-Chin,
Wang Li-Chuan,
Peng Chu-Ying,
Wang Ren-Ching
Publication year - 2012
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.26.1_supplement.840.8
Subject(s) - senescence , apoptosis , cell cycle , microbiology and biotechnology , cell cycle checkpoint , viability assay , dna damage , cell , biology , programmed cell death , in vivo , intracellular , chemistry , biochemistry , dna
Endothelial dysfunction remains one of the leading causes for the pathogenesis of cardiovascular diseases. tert‐butyl hydroperoxide (t‐BHP), a short‐chain lipid hydroperoxide analog, has been referred to cause cell injury in different systems. The study aimed to elucidate the effects of t‐BHP on oxidation‐induce apoptosis and cellular senescence and its possible mechanisms in rat aorta. Primary cultured endothelial cells were treated with vehicle or t‐BHP. Dose‐dependent manner of t‐BHP significantly reduced cell viability, augmented cell toxicity, increased DNA damage, initiated cell cycle arrest, provoked positive senescence‐associated beta‐galactosidase staining and apoptotic cells, as well as diminished the telomerase activity, precipitated the cell cycle and apoptosis sinaling regulatory proteins. Similarly, male rats at 6‐week of age were administrated with vehicle or t‐BHP and t‐BHP‐treated rats were characterized by luminal expansion and thickening of intima and media in thoracic aorta, induction of endothelium damage, and increase of aortic apoptosis and senescence‐positive staining. This in vivo and in vitro study showed t‐BHP impaired vascular cell survival at least partially through inhibition of cell cycle regulatory proteins as well as activation of intracellular signal of the apoptotic cascade and cellular senescence related signaling pathways.