Nishikawa K, Sato Y, Arai H, Inoue K
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biochim Biophys Acta. 1993 Sep 8;1169(3):257-63.
We previously showed that phosphatidylserine-containing liposomes (phosphatidylserine liposomes) are effectively metabolized and induce foam-cell formation in cultured macrophages (Nishikawa, K., Arai, H. and Inoue, K. (1990) J. Biol. Chem. 265, 5226-5231). When cultured mouse peritoneal macrophages were incubated with phosphatidylserine liposomes of different cholesterol content, cholesteryl esters were formed in the cells in proportion to the cholesterol content of the liposomes added to the culture. Cholesteryl esters were formed only when the cells took up more than a certain amount of cholesterol (approx. 160% above the basal cell level). Fatty acyl moiety derived from the exogenous phospholipids were utilized preferentially for cholesteryl ester formation. Once cholesterol as an acceptor is exhausted within cells, the acyl chain may be utilized for triacylglycerol formation. Not only exogenous lipid acyl chains but also endogenous phospholipid acyl chains were also utilized for cholesteryl ester and triacylglycerol formation under the present conditions, since the radioactivity in phospholipids was incorporated into both cholesteryl esters and triacylglycerols in macrophages whose endogenous phospholipids had been prelabeled with radioactive fatty acids. Among phospholipid classes, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol served as the acyl donor, whereas sphingomyelin and cardiolipin did not. Mobilization of acyl chains from endogenous phospholipids to the neutral lipid fraction was also observed during foam-cell formation induced by acetyl low-density lipoprotein. The substance(s) produced within cell in the process of foam-cell formation may trigger the acyl chain mobilization from endogenous phospholipids.
我们之前的研究表明,含磷脂酰丝氨酸的脂质体(磷脂酰丝氨酸脂质体)在培养的巨噬细胞中能有效代谢并诱导泡沫细胞形成(西川,K.,新井,H.和井上,K.(1990年)《生物化学杂志》265卷,5226 - 5231页)。当用不同胆固醇含量的磷脂酰丝氨酸脂质体孵育培养的小鼠腹腔巨噬细胞时,细胞内形成的胆固醇酯与添加到培养物中的脂质体胆固醇含量成比例。只有当细胞摄取的胆固醇超过一定量(约高于基础细胞水平160%)时,才会形成胆固醇酯。源自外源性磷脂的脂肪酰部分优先用于胆固醇酯的形成。一旦细胞内作为受体的胆固醇耗尽,酰基链可用于三酰甘油的形成。在当前条件下,不仅外源性脂质酰基链,而且内源性磷脂酰基链也用于胆固醇酯和三酰甘油的形成,因为在其内源性磷脂已用放射性脂肪酸预标记的巨噬细胞中,磷脂中的放射性被整合到胆固醇酯和三酰甘油中。在磷脂类别中(磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸和磷脂酰肌醇)作为酰基供体,而鞘磷脂和心磷脂则不是。在由乙酰低密度脂蛋白诱导的泡沫细胞形成过程中,也观察到了酰基链从内源性磷脂向中性脂质部分的转移。在泡沫细胞形成过程中细胞内产生的物质可能触发酰基链从内源性磷脂的转移。