STUDIES ON THE MECHANISM OF UPTAKE OF LOW-DENSITY LIPOPROTEIN-PROTEOGLYCAN COMPLEX IN MACROPHAGES

被引:12
作者
VIJAYAGOPAL, P
SRINIVASAN, SR
RADHAKRISHNAMURTHY, B
BERENSON, GS
机构
[1] LOUISIANA STATE UNIV, MED CTR, DEPT MED, CARDIOL SECT, 1542 TULANE AVE, NEW ORLEANS, LA 70112 USA
[2] LOUISIANA STATE UNIV, MED CTR, DEPT BIOCHEM, NEW ORLEANS, LA 70112 USA
关键词
LDL-PROTEOGLYCAN COMPLEX; MACROPHAGE METABOLISM; (MOUSE PERITONEAL MACROPHAGE);
D O I
10.1016/S0167-4889(97)90003-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Earlier, we (Vijayagopal, P. et al. (1988) Biochim. Biophys. Acta 960, 210) showed that mouse peritoneal macrophages metabolize low density lipoprotein (LDL)-proteoglycan complex by a receptor pathway distinct from the acetyl-LDL receptor. Further studies were conducted to probe further into the mechanism of LDL-proteoglycan complex uptake by macrophages. Both I-125-methyl-LDL-proteoglycan complex and I-125-LDL-proteoglycan complex were taken up and degraded by the cells to the same extent. Similarly, the ability of these ligands to stimulate cholesteryl ester synthesis was also indistinguishable. These results rule out the possibility of apoB,E receptor involvement in the uptake of LDL-proteoglycan complex in macrophages. Sodium fluoride, cytochalasin D and aggregated LDL inhibited degradation of the complex by 24%, 26% and 28%, respectively, indicating that phagocytosis is only a minor pathway for the uptake. Both binding and degradation of the complex were not inhibited by excess hyaluronic acid suggesting that ligand recognition was not through hyaluronic acid binding sites. As compared to acetyl-LDL, the cellular degradation of LDL-proteoglycan complex was retarded. Macrophages exhibited a rapid stimulation of [H-3]inositol trisphosphate (IP3) release and diacylglycerol production when incubated with LDL-proteoglycan complex. Furthermore, pertussis toxin produced a 62% inhibition of LDL-proteoglycan complex mediated IP3 release, suggesting that LDL-proteoglycan complex metabolism in macrophages is dependent upon the G-protein coupled signal transduction mechanism. These results show that receptor mediated endocytosis plays a major role in the metabolism of LDL-proteoglycan complex in macrophages.
引用
收藏
页码:291 / 297
页数:7
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