Monosialyl Ganglioside GM3 Decreases Apolipoprotein B‐100 Secretion in Liver Cells

ABSTRACT Some sialic acid‐containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B‐100 (Apo‐B)‐containing lipoproteins, because Apo‐B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)‐assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3. Thus, there should be some regulatory links between GM3 and GD3. In this study, exogenous and endogenous monosialyl GM3 has been examined how GM3 plays a role in ApoB secretion in Chang liver cells in a view point of MTP and ApoB degradation in the same cells. The level of GM3 ganglioside in the GM3 synthase gene‐transfected cells was increased in the cell extract, but not in the medium. In addition, GM3 synthase gene‐transfected cells showed a diminished secretion of TG‐enriched ApoB with a lower content of TG in the medium. Exogenous GM3 treatment for 24 h exerted a dose dependent inhibitory effect on ApoB secretion together with TG, while a liver‐specific albumin was unchanged, indicating that GM3 effect is limited to ApoB secretion. GM3 decreased the mRNA level of MTP gene, too. ApoB protein assembly dysregulated by GM3 indicates the impaired ApoB secretion is caused by a proteasome‐dependent pathway. Treatment with small interfering RNAs (siRNAs) decreased ApoB secretion, but GM3‐specific antibody did not. These results indicate that plasma membrane associated GM3 inhibits ApoB secretion, lowers development of atherosclerosis by decreasing the secretion of TG‐enriched ApoB containing lipoproteins, suggesting that GM3 is an inhibitor of ApoB and TG secretion in liver cells. J. Cell. Biochem. 118: 2168–2181, 2017. © 2017 Wiley Periodicals, Inc. Exogenous and endogenous GM3 inhibits the secretion of TG‐enriched ApoB containing lipoproteins. GM3 is an inhibitor of ApoB and TG secretion in liver cells.