Inhibition of apolipoprotein B secretion by taurocholate is controlled by the N-terminal end of the protein in rat hepatoma McArdle-RH7777 cells

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• 作者：Elzinga ; Baukje M. ; Baller ; Julius F.W. ; Mensenkamp ; Arjen R. ; Yao ; Zemin ; Agellon ; Luis B. ; et. al.
• 关键词：Very-low-density lipoprotein ; Apolipoprotein B ; McA-RH7777 ; Bile salt ; Taurocholate ; Degradation ; ALLN ; N-acetyl-leucyl-leucyl-norleucinal ; apo ; apolipoprotein ; apoA-1 ; apolipoprotein A1 ; BS ; bile salt ; cDNA ; complementary DNA ; CE ; cholesterylester ; CMV
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2003
• 出版时间：December 30, 2003
• 年：2003
• 卷：1635
• 期：2-3
• 页码：93-103
• 全文大小：434 K

文摘

Bile salts (BS) inhibit the secretion of apolipoprotein B (apoB) and triacylglycerol (TG) in primary rat, mouse and human hepatocytes and in mice in vivo. We investigated whether lipidation of apoB into a lipoprotein particle is required for this inhibitory action of BS. The sodium/taurocholate co-transporting polypeptide (Ntcp) was co-expressed in McArdle-RH7777 (McA-RH7777) cells stably expressing the full-length human apoB100 (h-apoB100, secreted as TG-rich lipoprotein particles) or carboxyl-truncated human apoB18 (h-apoB18, secreted in lipid-free form). The doubly transfected cell lines (h-apoB/r-Ntcp) effectively accumulated taurocholic acid (TC). TC incubation decreased the secretion of endogenous rat apoB100 (−50 % ) and h-apoB18 (−35 % ), but did not affect secretion of rat apoA-I. Pulse-chase experiments (³⁵S-methionine) indicated that the impaired secretion of radiolabeled h-apoB18 and h-apoB100 was associated with accelerated intracellular degradation. The calpain protease inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) partially inhibited intracellular apoB degradation but did not affect the amount of either h-apoB18 or h-apoB100 secreted into the medium, indicating that inhibition of apoB secretion by TC is not due to calpain-dependent proteasomal degradation. We conclude that TC does not inhibit apoB secretion by interference with its lipidation, but rather involves a mechanism dependent on the N-terminal end of apoB.