Palmitic acid promotes endothelial progenitor cells apoptosis via p38 and JNK mitogen-activated protein kinase pathways.
OBJECTIVE
Recent studies have demonstrated that palmitic acid (PA) could regulate endothelial progenitor cells (EPCs) function (migration, proliferation, survival and angiogenesis) via various signal pathways, but the effect of PA on EPCs apoptosis and associated mechanisms are still elusive.


METHODS
The human EPCs were obtained by Ficoll density gradient centrifugation and cultured in M199 medium containing rh-VEGF (30ng/mL), rh-b-FGF (6ng/mL) and 10% fetal bovine serum for 7 days. The adhesive EPCs were harvested, then challenged with different concentrations of PA (ranging from 0 to 800mumol/L) for 48h and 400 micromol/L PA for different time periods (ranging from 0 to 60h) after 12h synchronization with serum-free medium. The EPCs apoptosis was determined by flow cytometry, expression of caspase-3, phosphorylated ERK1/2, JNK and p38 mitogen-activated protein kinase (MAPK) were quantified by Western blot. The effect of PA on caspase-3 activity in the absence or presence of specific MAPK pathway inhibitors was determined by colorimetry.


RESULTS
PA increased EPCs apoptosis in a dose- and time-dependent manner, upregulated phosphorylated-p38 and -JNK, caspase-3 expression of EPCs while ERK expression was not affected. PA-induced EPCs apoptosis could be partly ameliorated by p38 inhibitor SB203580 and JNK inhibitor SP600125, but not by ERK1/2 inhibitor PD98059.


CONCLUSIONS
These findings suggested that PA promoted EPCs apoptosis via p38 and JNK MAPKs pathways.
Department of Cardiology, Second Hospital Affiliated to the Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China.
Hailong
H
Jiang
Chun
C
Liang
Xing
X
Liu
Qijun
Q
Jiang
Zhiqing
Z
He
Jianxiang
J
Wu
Xiaoming
X
Pan
Yusheng
Y
Ren
Min
M
Fan
Mei
M
Li
Zonggui
Z
Wu
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D013234:Stem Cells / Q000201:enzymology / Q000502:physiology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; C432165:pyrazolanthrone; D019308:Palmitic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one