Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a liver directed adenoviral gene transfer system was used to overexpress human PLTP in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice transgenic for the human apoA-I gene (HuApoA-ITg), were utilized. Five days after injection of the recombinant PLTP adenovirus, wild type mice showed a 4-fold increase in serum PLTP activity in (12.2+/-1.3 micromol/ml per h to 48.1+/-8.6 micromol/ml per h (+394%), P < 0.001). The PLTP overexpression induced significant reduction of serum cholesterol (2.46+/-0.08 to 0.69+/-0.42 mmol/l (-72%), P < 0.001), phospholipids (3.10+/-0.06 to 0.90+/-0.24 mmol/l (-71%), P < 0.01), and triglycerides (0.2+/-0.07 to 0.08+/-0.03 mmol/l (-69%), (P < 0.001). ApoA-I was hardly detectable in the serum. These lipid changes were due to a dramatic reduction of high density lipoprotein (HDL). The HuApoA-ITg mice displayed higher basal HDL level and PLTP activity. Adenovirus mediated PLTP overexpression in these mice resulted in a similar decrease of the lipid levels as that seen in the C57/B1 mice. However, the lipoprotein profile revealed a redistribution of HDL, with the appearance of larger buoyant HDL species. The results demonstrate that plasma phospholipid transfer protein in vivo causes high density lipoprotein (HDL) conversion and thereby plays a central role in HDL metabolism.
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PMID:Adenovirus mediated overexpression of human phospholipid transfer protein alters plasma HDL levels in mice. 964 56

We have devised a combined in vivo, ex vivo, and in vitro approach to elucidate the mechanism(s) responsible for the hypoalphalipoproteinemia in heterozygous carriers of a naturally occurring apolipoprotein A-I (apoA-I) variant (Leu(159) to Arg) known as apoA-I Finland (apoA-I(FIN)). Adenovirus-mediated expression of apoA-I(FIN) decreased apoA-I and high density lipoprotein cholesterol concentrations in both wild-type C57BL/6J mice and in apoA-I-deficient mice expressing native human apoA-I (hapoA-I). Interestingly, apoA-I(FIN) was degraded in the plasma, and the extent of proteolysis correlated with the most significant reductions in murine apoA-I concentrations. ApoA-I(FIN) had impaired activation of lecithin:cholesterol acyltransferase in vitro compared with hapoA-I, but in a mixed lipoprotein preparation consisting of both hapoA-I and apoA-I(FIN) there was only a moderate reduction in the activation of this enzyme. Importantly, secretion of apoA-I was also decreased from primary apoA-I-deficient hepatocytes when hapoA-I was co-expressed with apoA-I(FIN) following infection with recombinant adenoviruses, a condition that mimics secretion in heterozygotes. Thus, this is the first demonstration of an apoA-I point mutation that decreases LCAT activation, impairs hepatocyte secretion of apoA-I, and makes apoA-I susceptible to proteolysis leading to dominantly inherited hypoalphalipoproteinemia.
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PMID:Proteolytic degradation and impaired secretion of an apolipoprotein A-I mutant associated with dominantly inherited hypoalphalipoproteinemia. 1129 28