Arsenic trioxide induces the apoptosis in vascular smooth muscle cells via increasing intracellular calcium and ROS formation.
The present study was designed to investigate whether arsenic trioxide induced the apoptosis in rat mesenteric arterial smooth muscle cells (SMCs), which provides new insights into mechanisms of arsenic-related vascular diseases. Here, we found that arsenic trioxide significantly decreased the viability of SMCs in a dose-dependent manner. In addition, higher level of arsenic trioxide directly caused cellular necrosis. The Hoechst and AO/EB staining demonstrated that apoptotic morphological change was presented in SMCs exposed to arsenic trioxide. The TUNEL assay displayed that more positive apoptotic signal appeared in SMCs treated with arsenic trioxide. The following result showed that ROS formation was markedly increased in arsenic trioxide-treated SMCs. Pretreatment with N-acetylcysteine, an anti-oxidant reagent, obviously attenuated the enhancement of ROS production and the reduction of cell viability induced by arsenic trioxide in SMCs. Arsenic trioxide also enhanced free intracellular Ca(2+) level in SMCs. BAPTA also significantly prevented the increased intracellular Ca(2+) and decreased cell viability induced by arsenic trioxide in SMCs. These results suggested that arsenic trioxide obviously induced apoptosis in SMCs, and its mechanism was partially associated with intracellular ROS formation and free Ca(2+) increasing.
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
Jing-Xiu
JX
Li
Ya-Qi
YQ
Shen
Ben-Zhi
BZ
Cai
Jing
J
Zhao
Xiaopeng
X
Bai
Yan-Jie
YJ
Lu
Xue-Qi
XQ
Li
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced; D010087:Oxides / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D004533:Egtazic Acid; D007770:L-Lactate Dehydrogenase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000077237:Arsenic Trioxide; D002118:Calcium