Abstract
Apolipoprotein B (apoB), an apolipoprotein associated with very low density lipoproteins and the atherogenic low density lipoproteins (LDL), directs the metabolism of lipoprotein particles in plasma by interacting with the LDL receptor. Utilizing human intestinal biopsy organ cultures, we have studied the synthesis of intestinal apoB in man. Intestinal organ cultures from normal adults (n = 6) were incubated in the presence of protease inhibitors in media supplemented with [35S]methionine. Media from these cultures were evaluated by sequential NaDodSO4 polyacrylamide gel electrophoresis, radioautography, and Western blot analyses, and intestinal biopsies were studied using immunohistochemistry. The relative abundance of apoB-100 and apoB-48 mRNA was assessed using reverse transcriptase-polymerase chain reaction followed by primer extension. Although apoB-48 was the principal isoprotein that was newly synthesized by intestinal organ cultures, apoB-100 was also synthesized and secreted by human intestinal organ cultures with 16 +/- 3% of the intestinal apoB mRNA coding for apoB-100. These results establish that apoB-100 is produced by the human intestine. The synthesis of the atherogenic apoB-100 by the intestine has pathophysiologic implications for the development of diet-induced atherosclerosis.
Highlights
Apolipoprotein B, an apolipoprotein associated with very low density lipoproteins and the atherogenic low density lipoproteins (LDL), directs the metabolism of lipoprotein particles in plasma by interacting with the LDL receptor
The metabolism of lipoproteins is directed by the apolipoproteins at the aqueous-lipid interface of the lipoprotein particles
ApoB remains associated with the same lipoprotein particle in the circulation and is the only apolipoprotein that does not undergo exchange between lipoprotein particles [9, 32]
Summary
Apolipoprotein B (apoB), an apolipoprotein associated with very low density lipoproteins and the atherogenic low density lipoproteins (LDL), directs the metabolism of lipoprotein particles in plasma by interacting with the LDL receptor. Utilizing human intestinal biopsy organ cultures, we have studied the synthesis of intestinal apoB in man. * apoB-100 was synthesized and secreted by human intestinal organ cultures with 16 3% of the intestinal apoB mRNA coding for apoB-100. Supplementary key words apolipoproteins lipoproteins cholesterol diet polymerase chain reaction atherosclerosis apoB-100 isoprotein [4, 5], a smaller apoB isoprotein is secreted by the intestine in both rats [6] and humans [7]. We have evaluated the synthesis of apoB in human intestinal organ cultures. The data from these studies indicate that, in addition to apoB-48, both the mRNA and protein of apoB-100 are synthesized by the human intestine. In contrast with the human liver, which secretes predominately the 512 kDa
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