Selective Uptake from LDL Is Stimulated by Unsaturated Fatty Acids and Modulated by Cholesterol Content in the Plasma Membrane: Role of Plasma Membrane Composition in Regulating Non-SR-BI-Mediated Sel
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- 作者：Toru Seo ; Wanda Velez-Carrasco ; Kemin Qi ; Marni Hall ; Tilla S. Worgall ; Rebecca A. Johnson ; and Richard J. Deckelbaum
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：June 25, 2002
- 年：2002
- 卷：41
- 期：25
- 页码：7885 - 7894
- 全文大小：376K
- 年卷期：v.41,no.25(June 25, 2002)
- ISSN：1520-4995
文摘
We previously reported that unsaturated fatty acids stimulated low-density lipoprotein (LDL)particle uptake in J774 macrophages by increasing LDL receptor activity. Since free fatty acids (FFA)also change plasma membrane properties, a putative cholesteryl ester (CE) acceptor for selective uptake(SU), we questioned the ability of FFA to modulate SU from LDL. Using [3H]cholesteryl ether/125I-LDLto trace CE core and whole particle uptake, we found that oleic acid and eicosapentaenoic acid, but notsaturated stearic acid, increased SU by 30% over control levels. An ACAT inhibitor, Dup128, abolishedFFA effects on SU, indicating that increased SU by FFA was secondary to changes in cell-free cholesterol(FC). Consistent with these observations, ACAT inhibition increased cell FC and reduced LDL SU byhalf. The important role of plasma membrane composition was further demonstrated in that 
-cyclodextrin-(-CD-) mediated FC removal from the plasma membrane increased SU from LDL and was furtherstimulated by U18666A, a compound that inhibits FC transport between lysosomes and the plasmamembrane. In contrast, cholesterol-saturated -CD markedly reduced LDL SU. In contrast to LDL SU,oleic acid, ACAT inhibition, U18666A, or -CD had no effects on HDL SU. Moreover, HDL SU wasinhibited by antimouse SR-BI antibody by more than 50% but had little effect on LDL SU. In C57BL/6mice fed a high fat diet, plasma FFA levels increased, and SU accounted for an almost 4-fold increasedproportion of total cholesterol delivery to the arterial wall. Taken together, these data suggest that LDLSU is mediated by pathways independent of SR-BI and is influenced by plasma membrane FC content.Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an important mechanismfor cholesterol delivery in vivo.
-cyclodextrin-(-CD-) mediated FC removal from the plasma membrane increased SU from LDL and was furtherstimulated by U18666A, a compound that inhibits FC transport between lysosomes and the plasmamembrane. In contrast, cholesterol-saturated -CD markedly reduced LDL SU. In contrast to LDL SU,oleic acid, ACAT inhibition, U18666A, or -CD had no effects on HDL SU. Moreover, HDL SU wasinhibited by antimouse SR-BI antibody by more than 50% but had little effect on LDL SU. In C57BL/6mice fed a high fat diet, plasma FFA levels increased, and SU accounted for an almost 4-fold increasedproportion of total cholesterol delivery to the arterial wall. Taken together, these data suggest that LDLSU is mediated by pathways independent of SR-BI and is influenced by plasma membrane FC content.Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an important mechanismfor cholesterol delivery in vivo.