Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/33144
標題: Humic Acid Induces G1 Phase Arrest and Apoptosis in Cultured Vascular Smooth Muscle Cells
作者: Hseu, Y.C.
廖俊旺
Lin, E.
Chen, J.Y.
Liua, Y.R.
Huang, C.Y.
Lu, F.J.
Liao, J.W.
Chen, S.C.
Yang, H.L.
關鍵字: humic acid
cell cycle arrest
apoptosis
smooth muscle cells
vein endothelial-cells
breast-cancer cells
blackfoot-disease
dna-damage
poly(adp-ribose) polymerase
cardiovascular-system
antrodia-camphorata
human erythrocytes
plaque stability
cycle control
期刊/報告no:: Environmental Toxicology, Volume 24, Issue 3, Page(s) 243-258.
摘要: Humic acid (HA) in well water used by the inhabitants for drinking is one of the possible etiological factors for Blackfoot disease (BFD). In this study, the ability of HA to inhibit cell cycle progression and induce apoptosis in cultured smooth muscle cells (SMCs; A7r5) was investigated. Treatment of the SMCs at various HA concentrations (25-200 mu g/mL) resulted in sequences of events marked by apoptosis, as shown by loss of cell viability, morphology change, and internucleosomal DNA fragmentation. HA-induced apoptotic cell death that is associated with loss of mitochondrial membrane potential (Delta Psi m), cytochrome c translocation, caspase-3, -8, and -9 activation, poly ADP-ribose polymerase (PARP) degradation, dysregulation of Bcl-2 and Bax, and upregulation of p53 and phospholyrated p53 (p-p53) in SMCs. Flow cytometry analysis demonstrated that HA blocked cell cycle progress in the G1 phase in SMCs. This blockade of cell cycle was associated with reduced amounts of cyclin D1, CDK4, cyclin E, CDK2, and hyperphosphorylated retinoblastoma protein (pRb) in a time-dependent manner. Apparent DNA strand breaks (DNA damage) were also detected in a dose-dependent manner using Single-cell gel electrophoresis assay (comet assay). Furthermore, HA induced dose-dependent elevation of reactive oxygen species (ROS) level in SMCs, and antioxidant vitamin C and Trolox effectively suppressed HA-induced DNA damage and dysregulation of Bcl-2/Bax. Our findings suggest that HA-induced DNA damage, cell cycle arrest, and apoptosis in SMCs may be an underlying mechanisms for the atherosclerosis and thrombosis observed in the BFD endemic region. (C) 2008 Wiley Periodcals, Inc. Environ Toxicol 24: 243-258, 2009.
URI: http://hdl.handle.net/11455/33144
ISSN: 1520-4081
文章連結: http://dx.doi.org/10.1002/tox.20426
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