Role of c-fos gene in vasoactive intestinal peptide promoted synthesis of pulmonary surfactant phospholipids.
We previously reported that vasoactive intestinal peptide (VIP) promoted synthesis of phosphatidylcholine (PC) in alveolar type II (ATII) cells. But the intracellular mechanism for this effect was unknown. In this work, we investigated the intracellular signal transduction pathway for VIP promoted synthesis of PC, the major lipid component of pulmonary surfactant (PS), by using an antagonist of VIP receptors, inhibitor of protein kinase C (PKC) and antisense oligonucleotides (AS-ODN) for c-fos oncogene. Our results showed that: 1 in circle [D-P-Cl-Phe(6)-Leu(17)]-VIP (10(-6) mol/l), an antagonist of VIP receptors, could decrease the quantity of [(3)H] choline incorporation, microsomal choline-phosphate cytidylyltransferase (CCT) mRNA expression and CCT activity induced by VIP (10(-8) mol/l) in cultured lung explants to the control levels; 2 in circle VIP (10(-8) mol/l) upregulated c-Fos protein expression in ATII cells. AS-ODN for c-fos oncogene (9x10(-6) mol/l) could block the elevation of [(3)H] choline incorporation, microsomal CCT mRNA expression and CCT activity induced by VIP in cultured lung explants and in ATII cells; 3 in circle H7 (10(-5) mol/l), a PKC inhibitor could also reduce VIP induced [(3)H] choline incorporation, microsomal CCT mRNA expression and CCT activity in cultured lung explants and in ATII cells. These results demonstrated that VIP receptors, PKC and c-Fos protein played important roles in the signaling pathway through which VIP promoted the synthesis of PC.
Li
Lian
L
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, PR, China.
She
Hua
H
Yue
Shao-Jie
SJ
Qin
Xiao-Qun
XQ
Guan
Cha-Xiang
CX
Liu
Hui-Jun
HJ
Luo
Zi-Qiang
ZQ
D000818:Animals; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010713:Phosphatidylcholines / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D011493:Protein Kinase C; D019916:Choline-Phosphate Cytidylyltransferase