Inhibition of ADP-ribosylation suppresses aberrant accumulation of lipidated apolipoprotein B in the endoplasmic reticulum

Abstract

ApoB-crescent, an endoplasmic reticulum (ER)-lipid droplet amalgamation structure, is a useful marker to indicate aberrant lipidated apolipoprotein B accumulation in the hepatocyte ER. Blockade of the ER-to-Golgi transport by either vesicle transport inhibitors or dominant-negative Arf1 caused a significant increase in ApoB-crescents. However, a low concentration of Brefeldin A induced the same result without affecting protein secretion, suggesting ADP-ribosylation as an additional mechanism. ADP-ribosylation inhibitors not only suppressed the increase of ApoB-crescents, but also rapidly dissolved existing ApoB-crescents. These results implicate the involvement of ADP-ribosylation in the ApoB-crescent formation and maintenance process at the ER.

Keywords: 4,6-diamidino-2-phenylindole; ADP; ADP-ribosylation; ADP-ribosylation factor 1; ALLN; ApoB; ApoB-crescent; Arf1; BFA; Brefeldin A; DAPI; DHA; ER; GDP; GEF; GTP; LD; LPDS; Lipid droplet; MIBG; MTP; N-acetyl-l-leucyl-l-leucyl-l-norleucinal; NAM; NDGA; OA; VLDL; adenosine diphosphate; apolipoprotein B-100; brefeldin A; docosahexaenoic acid; endoplasmic reticulum; guanine diphosphate; guanine nucleotide exchange factor; guanine triphosphate; lipid droplet; lipoprotein deficient serum; m-iodobenzylguanidine hemisulfate salt; microsomal triglyceride transfer protein; nicotinamide; nordihydroguaiaretic acid; oleic acid; very low-density lipoprotein.