Protein kinase C-alpha activation induces NF-kB-dependent VCAM-1 expression in cultured human umbilical vein endothelial cells treated with sera from preeclamptic patients.
OBJECTIVE
To determine if activation of the NF-kappaB-VCAM-1 pathway is mediated by protein kinase C-alpha (PKC-alpha).


METHODS
PKC inhibitor polymyxin B was added to cultured human umbilical vein endothelial cells (HUVECs) from normal pregnancies. Sera from women with uncomplicated pregnancies and with preeclampsia (PE) were added to the control and intervention groups of the HUVECs. Cytoplasmic and membrane PKC, cytoplasmic NF-kappaB inhibitory factor (I-kappaB), and NF-kappaBp65 were measured. Cell viability, cell apoptosis, and VCAM-1 expression were determined.


RESULTS
Cytoplasmic PKC and I-kappaB in HUVECs incubated with sera from women with PE were significantly lower than in the control group, and the PKC content of the cell membrane, NF-kappaBp65, the expression of VCAM-1, and cell apoptosis were higher than in the normal pregnancy group. Cell viability was lower in the intervention than the control group. When HUVECs were pretreated with PKC inhibitor polymyxin B, the cytoplasmic PKC and I-kappaB content of the HUVECs increased in the PE group; the PKC content of the cell membrane, NF-kappaBp65, the expression of VCAM-1 and cell apoptosis decreased. Cell viability increased.


CONCLUSIONS
Activation of the PKC-NF-kappaB signaling pathway may play an important role in the injury of HUVECs in women with PE.
Jiang
Rongzhen
R
Department of Obstetrics and Gynecology, Shanghai Jiaotong University No. 6 People's Hospital, Shanghai, China.
Teng
Yincheng
Y
Huang
Yajuan
Y
Gu
Jinghong
J
Li
Min
M
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D002470:Cell Survival / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018709:Statistics, Nonparametric; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology
D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D051571:Protein Kinase C-alpha; D011112:Polymyxin B