Intestinal and hepatic apolipoprotein B gene expression in abetalipoproteinemia.
A 20-year-old woman with abetalipoproteinemia underwent orthotopic liver transplantation for cirrhosis, affording access to her liver and small intestine for study. Before transplantation, her plasma apolipoprotein B concentration was less than 1 mg/dL according to enzyme-linked immunosorbent assay, whereas after transplantation her plasma apolipoprotein B concentration was 76 mg/dL (all apolipoprotein B-100). Apolipoprotein B content was reduced in her intestine and liver compared with normal and cirrhotic controls. Cultured hepatocytes from the patient's explanted liver secreted a 1.006 g/mL less than or equal to d less than or equal to 1.063 g/mL lipoprotein rich in apolipoprotein E and a 1.063 g/mL less than or equal to d less than or equal to 1.21 g/mL lipoprotein containing apolipoproteins E and A-I with no immunodetectable apolipoprotein B in the culture medium. Normal hepatocytes secreted very low-density lipoprotein and low-density lipoprotein containing apolipoprotein B-100. Abetalipoproteinemic intestinal apolipoprotein B messenger RNA concentration was 4-5-fold higher than control values. However, the patient's liver apolipoprotein B messenger RNA level was one fifth that of control normal and cirrhotic liver. Analysis of the patient's intestinal and hepatic apolipoprotein B messenger RNA for posttranscriptional stop-codon insertion revealed normally edited transcripts. These results suggest that apolipoprotein B is synthesized as the product of a normally edited messenger RNA transcript, but not secreted, in abetalipoproteinemia.
Black
D D
DD
Department of Pediatrics, University of Chicago Medical Center, Illinois.
Hay
R V
RV
Rohwer-Nutter
P L
PL
Ellinas
H
H
Stephens
J K
JK
Sherman
H
H
Teng
B B
BB
Whitington
P F
PF
Davidson
N O
NO
D000012:Abetalipoproteinemia / Q000235:genetics* / Q000601:surgery; D000328:Adult; D001053:Apolipoproteins / Q000032:analysis; D001055:Apolipoproteins B / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D001055:Apolipoproteins B; D009841:Oligonucleotides; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol