TY - JOUR
T1 - Hepatic expression of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (apobec-1) ameliorates hypercholesterolemia in LDL receptor-deficient rabbits
AU - Kozarsky, Karen F.
AU - Bonen, Denise K.
AU - Giannoni, Federico
AU - Funahashi, Toru
AU - Wilson, James M.
AU - Davidson, Nicholas O.
PY - 1996/5/20
Y1 - 1996/5/20
N2 - Apolipoprotein (apo) B48, a protein contained in intestinally derived lipoprotein particles, is synthesized by post-transcriptional editing of apoB100 mRNA. This reaction is mediated by an enzyme complex that includes the catalytic subunit, apobec-1. The liver of most mammals, by contrast, contains only unedited apoB mRNA and secretes apoB100, the major protein component of plasma low-density lipoprotein (LDL). Because rabbits, like humans, fail to edit hepatic apoB100 mRNA, we introduced a recombinant adenovirus encoding apobec-1 into the livers of LDL receptor-defective rabbits to determine the impact on lipoprotein metabolism of hepatic apoB48 secretion. Transgene expression was mainly confined to the liver and was sustained for up to 3 weeks following virus administration, as evidenced by the presence of apobec-1 mRNA and the ability of hepatic S100 extracts to edit a synthetic apoB RNA template in vitro. The transient induction of hepatic apoB mRNA editing accompanied alterations in very-low-density lipoprotein (VLDL) size, the presence of apoB48 in fractions spanning the VLDL and LDL range, and modest reductions in total plasma cholesterol levels.
AB - Apolipoprotein (apo) B48, a protein contained in intestinally derived lipoprotein particles, is synthesized by post-transcriptional editing of apoB100 mRNA. This reaction is mediated by an enzyme complex that includes the catalytic subunit, apobec-1. The liver of most mammals, by contrast, contains only unedited apoB mRNA and secretes apoB100, the major protein component of plasma low-density lipoprotein (LDL). Because rabbits, like humans, fail to edit hepatic apoB100 mRNA, we introduced a recombinant adenovirus encoding apobec-1 into the livers of LDL receptor-defective rabbits to determine the impact on lipoprotein metabolism of hepatic apoB48 secretion. Transgene expression was mainly confined to the liver and was sustained for up to 3 weeks following virus administration, as evidenced by the presence of apobec-1 mRNA and the ability of hepatic S100 extracts to edit a synthetic apoB RNA template in vitro. The transient induction of hepatic apoB mRNA editing accompanied alterations in very-low-density lipoprotein (VLDL) size, the presence of apoB48 in fractions spanning the VLDL and LDL range, and modest reductions in total plasma cholesterol levels.
UR - http://www.scopus.com/inward/record.url?scp=0029936990&partnerID=8YFLogxK
U2 - 10.1089/hum.1996.7.8-943
DO - 10.1089/hum.1996.7.8-943
M3 - Article
C2 - 8727508
AN - SCOPUS:0029936990
SN - 1043-0342
VL - 7
SP - 943
EP - 957
JO - Human Gene Therapy
JF - Human Gene Therapy
IS - 8
ER -