Apolipoprotein serum amyloid A down-regulates smooth-muscle cell lipid biosynthesis.
The addition of acute-phase apolipoprotein serum amyloid A (SAA) to cultured aortic smooth-muscle cells caused a decrease in the incorporation of [(14)C]acetate into lipids. Optimal inhibition of lipid biosynthesis was achieved with 2 microM SAA, and the effect was maintained for up to 1 week when SAA was included in the culture medium. Lipid extracts were subjected to TLC and it was determined that the SAA-induced decrease in [(14)C]acetate incorporation into lipids was attributable to decreases in cholesterol, phospholipid and triglyceride levels. The accumulated mass of cholesterol and phospholipid in SAA-treated cultures was significantly less than that of controls, with no change in the accumulated protein. Moreover, SAA had no effect on either protein synthesis or DNA synthesis, suggesting that SAA specifically alters lipid synthesis. By using a peptide corresponding to the cholesterol-binding domain of acute-phase SAA (amino acids 1-18), it was shown that this region of the molecule was as effective as the full-length protein in decreasing lipid synthesis and the accumulation of cholesterol and phospholipid. The implications of these findings for atherosclerosis and Alzheimer's disease are discussed.
Schreiber
B M
BM
Department of Biochemistry, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA. schreibe@biochem.bumc.bu.edu
Veverbrants
M
M
Fine
R E
RE
Blusztajn
J K
JK
Salmona
M
M
Patel
A
A
Sipe
J D
JD
D019342:Acetic Acid / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010743:Phospholipids / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis
D008055:Lipids; D010446:Peptide Fragments; D010743:Phospholipids; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol; D019342:Acetic Acid