Dixon J L, Ginsberg H N
Department of Food Science and Human Nutrition, University of Missouri, Columbia 65211.
J Lipid Res. 1993 Feb;34(2):167-79.
A major theme of this review is that apoB secretion is regulated post-translationally, and that apoB secretion reacts rapidly to the current state of lipid metabolism in the cell. Therefore, as discussed by Fungwe et al. (122), the metabolism of triglyceride and of cholesteryl ester, in so far as both can be used as core lipids for apoB-containing LPs, are inextricably linked, and the shortage of one or both of these lipids could, by "allowing" increased intracellular degradation in the ER, inhibit the secretion of apoB. Another theme in this review is that the regulation of apoB secretion may be quite different in rat hepatocytes compared to cultured cells (HepG2) used as a model for human hepatocytes. Exogenous fatty acids appear to modulate the rate of apoB secretion in HepG2 cells, whereas they have only minimal effects on apoB secretion in rat hepatocytes or liver. Increased dietary cholesterol, on the other hand, appears to be an important modulator of apoB secretion in rats, but the evidence for effects of cholesterol on apoB secretion in HepG2 cells is less convincing. Finally, because HepG2 cells are an immortalized cell line, there could be many differences between these cells and human hepatocytes in vivo. Therefore, many of the results obtained with HepG2 cells should be corroborated in primary cultures of human hepatocytes. However, investigators utilizing primary human hepatocytes should be sure that the culture conditions are adequate to maintain the continued transcription of liver specific genes and to prevent the dedifferentiation of these cells in culture (85, 86).
本综述的一个主要主题是载脂蛋白B（apoB）的分泌在翻译后受到调控，并且apoB分泌对细胞内脂质代谢的当前状态反应迅速。因此，正如Fungwe等人（122）所讨论的，甘油三酯和胆固醇酯的代谢，就它们都可作为含apoB脂蛋白的核心脂质而言，是紧密相连的，而这两种脂质中一种或两种的短缺可能通过“允许”内质网中细胞内降解增加来抑制apoB的分泌。本综述的另一个主题是，与用作人类肝细胞模型的培养细胞（HepG2）相比，大鼠肝细胞中apoB分泌的调控可能有很大不同。外源性脂肪酸似乎可调节HepG2细胞中apoB的分泌速率，而它们对大鼠肝细胞或肝脏中apoB分泌的影响极小。另一方面，饮食中胆固醇增加似乎是大鼠中apoB分泌的重要调节因素，但胆固醇对HepG2细胞中apoB分泌影响的证据则不那么令人信服。最后，由于HepG2细胞是永生化细胞系，这些细胞与体内人类肝细胞之间可能存在许多差异。因此，许多用HepG2细胞获得的结果应在人类肝细胞原代培养中得到证实。然而，使用人类原代肝细胞的研究人员应确保培养条件足以维持肝脏特异性基因的持续转录，并防止这些细胞在培养中去分化（85, 86）。
