Suppressing phosphatidylcholine-specific phospholipase C and elevating ROS level, NADPH oxidase activity and Rb level induced neuronal differentiation in mesenchymal stem cells.
In the previous research, we found that D609 (tricyclodecan-9-yl-xanthogenate) could induce human marrow stromal cell (hMSC) differentiation to neuron-like cells. In this study, to understand the possible mechanism, we sequentially investigated the changes of phosphatidylcholine-specific phospholipase C (PC-PLC) activity, the expression of Rb, the intracellular reactive oxygen species (ROS) levels, NADPH oxidase and superoxide dismutase (SOD) activities when D609 induced neuronal differentiation in rat mesenchymal stem cells (MSCs). The results showed that D609 obviously inhibited the activity of PC-PLC when it induced neuronal differentiation in rat MSCs. Simultaneously, ROS level and the activity of NADPH oxidase increased significantly, but the MnSOD and Cu/ZnSOD activities were not altered. Furthermore, the level of Rb protein was evidently elevated. Our data suggested that PC-PLC mediated neuronal differentiation of rat MSCs by elevating NADPH oxidase activity, ROS level, and up-regulating the expression of Rb protein.
Wang
Nan
N
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China.
Xie
Kun
K
Huo
Siwei
S
Zhao
Jing
J
Zhang
Shangli
S
Miao
Junying
J
D000818:Animals; D015153:Blotting, Western; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001952:Bridged-Ring Compounds; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D019255:NADPH Oxidases; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C