LENGTHS OF TRUNCATED FORMS OF APOLIPOPROTEIN-B (APO-B) DETERMINE THEIR INTESTINAL PRODUCTION

被引:21
作者
KRUL, ES [1 ]
TANG, JJ [1 ]
KETTLER, TS [1 ]
CLOUSE, RE [1 ]
SCHONFELD, G [1 ]
机构
[1] WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV ATHEROSCLEROSIS,4566 SCOTT AVE,BOX 8046,ST LOUIS,MO 63110
关键词
D O I
10.1016/0006-291X(92)92313-M
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Most truncations of apoB associated with hypobetalipoproteinemia (HBL) result from frame shift mutations of the apoB gene that give rise to premature stop codons and truncations of C-terminal sequences. The "natural" truncation, apoB-48, arises from a stop codon by cotranscriptional editing of intestinal apoB-100 mRNA. We hypothesized that mutant apoB mRNA would be normally edited and that only those apoB truncations shorter than apoB-48 would be expressed in enterocytes, because translation of mRNAs giving rise to longer truncations would be interrupted by the apoB-48 stop codon. Duodenal mucosal biopsies from HBL and normolipidemic subjects were incubated with [35S]methionine, apoB was immunoprecipitated and bands were visualized by autoradiography. Biopsies of three subjects heterozygous for apoB-54.8 or apoB-89 synthesized virtually only apoB-48. By contrast, the biopsy of a subject heterozygous for apoB-40 synthesized both apoB-48 and apoB-40. Thus, enterocytes in HBL edit the mutant mRNAs similarly to the apoB mRNA of normal enterocytes and the small intestine of heterozygotes with truncations longer than apoB-48 produce only apoB-48, as the apoB-48 stop codon terminates translation proximal to the mutant stop codon. By contrast, intestines of heterozygotes with truncations shorter than apoB-48 produce the truncated apoB because the mutant stop codon stops translation before the apoB-48 stop codon. In conclusion, only the liver secretes apoB truncations larger than apoB-48, whereas shorter truncations are secreted by both liver and intestine. © 1992.
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页码:1069 / 1076
页数:8
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