Reactive oxygen species mediate oxidized low-density lipoprotein-induced inhibition of oct-4 expression and endothelial differentiation of bone marrow stem cells.
This study was to test the hypothesis that oxidized low-density lipoprotein (ox-LDL) modified the behavior of bone marrow stem cells, including proliferation, Oct-4 expression, and their endothelial differentiation through reactive oxygen species (ROS) formation in vitro. Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL with or without the antioxidant N-acetylcysteine (NAC). Ox-LDL generated a significant amount of ROS in the culture system as measured with electron paramagnetic resonance spectroscopy, and substantially inhibited the proliferation, Oct-4 expression, and endothelial differentiation of MAPCs. ROS production from ox-LDL in the culture system was completely prevented by NAC (1 mM). NAC treatment completely restored endothelial differentiation potential of MAPCs that was diminished by low-dose ox-LDL. NAC also significantly, but not completely, reversed the inhibitory effect of ox-LDL on proliferation and Oct-4 expression in MAPCs. NAC treatment only slightly restored Akt phosphorylation impaired by ox-LDL in the cells. ROS formation was important in the action of ox-LDL on MAPCs, including Oct-4 expression, proliferation, and endothelial differentiation. However, other mechanism(s) like Akt signaling and apoptosis might also play a critical role in mediating the effect of ox-LDL on these cells.
Lu
Tiewei
T
The Children's Hospital of Chongqing Medical University , Chongqing, China.
Parthasarathy
Sampath
S
Hao
Hong
H
Luo
Min
M
Ahmed
Shabnam
S
Zhu
Jing
J
Luo
Suxin
S
Kuppusamy
Periannan
P
Sen
Chandan K
CK
Verfaillie
Catherine M
CM
Tian
Jie
J
Liu
Zhenguo
Z
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D008077:Lipoproteins, LDL; D050814:Octamer Transcription Factor-3; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D000111:Acetylcysteine