Gene expression profiling of the proliferative effect of periplocin on mouse cardiac microvascular endothelial cells.
OBJECTIVE
Periplocin is an active digitalis-like component from Cortex Periplocae, which has been widely used in the treatment of heart diseases in China for many years. According to the recommendations on the cardiovascular effect of periplocin from in vivo experiments, subsequent in vitro experiments are greatly needed for the global assessment of periplocin. The objective of this study is to investigate the cell proliferation effect and the mechanism of periplocin on endothelial cells.


METHODS
The proliferative activity of periplocin (0.4, 2, 10, 50, 250 micromol/L; 6, 12, 24, 48, 72 h) was investigated by a comparison with the well-reported cardiac glycoside, ouabain, on mouse cardiac microvascular endothelial cells (CMEC). 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and 5-bromo-2-deoxyuridine (BrdU) assays were used to evaluate cell proliferation and viability. Subsequently, cDNA microarray experiments were performed on periplocin- (50 micromol/L) and ouabain- (50 micromol/L) treated cells, and data was analyzed by ArrayTrack software.


RESULTS
Periplocin could increase cell viability to a level lower than ouabain in the MTT analysis, but decrease LDH release simultaneously. The BrdU incorporation assay showed an increase in cell proliferation with 2-50 micromol/L periplocin. Genes related to protein serine/threonine kinase were the most significantly enriched in the 160 genes identified in periplocin versus the control. In the 165 genes regulated by periplocin versus ouabain, GTP-binding was the most altered term.


CONCLUSIONS
The results demonstrated the proliferation action of periplocin on CMEC. Meanwhile, its lower cytotoxicity compared to ouabain provides a new insight into the treatment of heart failure.
Wang
Xiao-ying
XY
Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Gao
Xiu-mei
XM
Liu
Hong
H
Zhang
Han
H
Liu
Yang
Y
Jiang
Min
M
Hu
Li-min
LM
Zhang
Bo-li
BL
D000818:Animals; D000831:Animals, Newborn; D002301:Cardiac Glycosides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010042:Ouabain / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D012503:Saponins; C502381:periplocin; D010042:Ouabain