Arsenic trioxide induces the apoptosis in bone marrow mesenchymal stem cells by intracellular calcium signal and caspase-3 pathways.
It was previously reported that excessive arsenic trioxide would produce cardiovascular toxicity. Bone marrow mesenchymal stem cells (BMSCs) have been shown to play a supporting role in cardiovascular functions. The increasing apoptosis of BMSCs commonly would promote the development of cardiovascular diseases. Thus we hypothesize that arsenic trioxide caused apoptosis in BMSCs, which provided a better understanding of arsenic toxicity in hearts. The present study was designed to investigate the proapoptotic effects of arsenic trioxide on BMSCs and explore the mechanism underlying arsenic trioxide-induced BMSCs apoptosis. We demonstrate that arsenic trioxide significantly inhibited survival ratios of BMSCs in a concentration-dependent and time-dependent manner. The Annexin V/PI staining and terminal deoxynucleotidyl transferasemediated dUTP nick-end labelling (TUNEL) assay also showed that arsenic trioxide markedly induced the apoptosis of BMSCs. The caspase-3 activity was obviously enhanced in the presence of arsenic trioxide in a concentration-dependent manner in BMSCs. Additionally, arsenic trioxide caused the increase of intracellular free calcium ([Ca(2+)](i)) in rat BMSCs. BAPTA pretreatment may attenuate the apoptosis of BMSCs induced by arsenic trioxide. Taken together, arsenic trioxide could inhibit the proliferation and induce the apoptosis of BMSCs by modulating intracellular [Ca(2+)](i), and activating the caspase-3 activity.
Cai
Ben-Zhi
BZ
Department of Pharmacology, Harbin Medical University, Baojian Road 157, Harbin 150081, China.
Meng
Fan-Yu
FY
Zhu
Song-Ling
SL
Zhao
Jing
J
Liu
Jia-Qi
JQ
Liu
Chan-Juan
CJ
Chen
Nan
N
Ye
Ming-Lei
ML
Li
Zhong-Yu
ZY
Ai
Jing
J
Lu
Yan-Jie
YJ
Yang
Bao-Feng
BF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001152:Arsenicals; D010087:Oxides; D053148:Caspase 3; D000077237:Arsenic Trioxide; D002118:Calcium