Vascular endothelial growth factor gene expression regulated by protein kinase C pathway in endothelial cells during hypoxia.
Objective. To investigate the relationship between Vascular endothelial growth factor (VEGF) gene expression and protein kinase C (PKC) activity. Method. 1) Rat's primary pulmonary artery endothelial cells (PAEC) were cultured under hypoxia condition (1% O2). Changes of PKC activity and VEGF mRNA in PAEC were detected at 0 (control), 1, 3, 6, and 12 h in the hypoxic condition of culture. 2) After addition of PKC inhibitor (staurosporine) in culture medium and culturing PAEC in hypoxic condition immediately, PKC activity and VEGF mRNA in PAEC were measured at the same time. VEGF protein in culture medium under the two conditions above were also detected. Result. PKC activity in PAEC were obviously elevated at 1 h during hypoxia as compared with the control (P<0.05); VEGF mRNA expression in PAEC and VEGF protein level in culture medium were increased significantly (P<0.01) at 3 h and 6 h during hypoxia respectively as compared with the control (P<0.01); After addition of PKC inhibitor in culture medium and culturing cells in hypoxia condition immediately, PKC activity in PAEC decreased significantly as compared with that at 0 h (P<0.01), and there were no significant changes of VEGF mRNA in PAEC and VEGF protein level in culture medium at any time (P>0.05). Conclusion. The results demonstrate that hypoxia stimulates pulmonary arterial vascular endothelial cells to secrete VEGF, and PKC may be one of the factors that up-regulate VEGF gene expression during hypoxia.
Zhou
Zhi
Z
Cardiology Department, Naval General Hospital, Beijing. VEGF@263.net
Yang
Xi-ming
XM
Xie
Yin-zhi
YZ
Yin
Zhao-yun
ZY
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011493:Protein Kinase C; D019311:Staurosporine