Very low density lipoproteins stimulate surfactant lipid synthesis in vitro.
Surfactant synthesis is critically dependent on the availability of fatty acids. One fatty acid source may be circulating triglycerides that are transported in VLDL, and hydrolyzed to free fatty acids by lipoprotein lipase (LPL). To evaluate this hypothesis, we incubated immortalized or primary rat alveolar pre-type II epithelial cells with VLDL. The cells were observed to surface bind, internalize, and degrade VLDL, a process that was induced by exogenous LPL. LPL induction of lipoprotein uptake significantly increased the rates of choline incorporation into phosphatidylcholine (PC) and disaturated PC, and these effects were associated with a three-fold increase in the activity of the rate-regulatory enzyme for PC synthesis, cytidylyltransferase. Compared with native LPL, a fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL did not activate CT despite inducing VLDL uptake. A variant of the fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL that partially blocked LPL-induced catabolism of VLDL via LDL receptors also partially blocked the induction of surfactant synthesis by VLDL. Taken together, these observations suggest that both the lipolytic actions of LPL and LPL-induced VLDL catabolism via lipoprotein receptors might play an integral role in providing the fatty acid substrates used in surfactant phospholipid synthesis.
Mallampalli
R K
RK
Department of Internal Medicine, Department of Veterans Affairs Medical Center, The University of Iowa College of Medicine, Iowa City 52242, USA.
Salome
R G
RG
Bowen
S L
SL
Chappell
D A
DA
D000818:Animals; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism / Q000494:pharmacology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism
D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D008071:Lipoprotein Lipase