Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human apolipoprotein (apo) B plays an obligatory role in the assembly and secretion of hepatic triglyceride-rich lipoproteins. Investigation of the truncated human apoB variants associated with hypobetalipoproteinemia has suggested that both size and secretion of apoB-containing lipoproteins may be reduced by carboxyl-terminal truncation. To examine the role of the carboxyl terminus of apoB in the assembly and secretion of hepatic lipoproteins, we have generated rat hepatoma McA-RH7777 cells that synthesize and secrete the full-length human apoB100 and the truncated forms B94, B88, B80, B72, and B60. In the resulting lipoproteins, particle density was inversely related to the logarithm of apoB length, ranging from 1.019 g/ml for apoB100 to 1.06 g/ml for B60. Furthermore, particle diameter (as determined by non-denaturing gel electrophoresis) was directly correlated with apoB length, ranging from 21.4 nm for apoB100 to 17.7 nm for B60. The relationship between apoB length and particle geometry was best defined by a linear correlation between length and core volume; a 10% decrease in apoB length resulted in an approximately 13% decrease in core volume. These observations, which are in agreement with the observations of aberrant lipoproteins in hypobetalipoproteinemia, suggest that lipid recruitment by apoB is progressively reduced by carboxyl-terminal truncation. However, pulse-chase studies indicated that carboxyl-terminal truncation did not impair apoB secretion. The recombinant human apoB forms were secreted as efficiently as endogenous rat apoB100; approximately 20% of total newly synthesized apoB72, B80, or B100 was secreted at the end of the chase. Intracellular degradation of newly synthesized apoB was observed for both the truncated human and the endogenous rat proteins. These data suggest that the low apoB levels in hypobetalipoproteinemia might not be caused by impaired secretion of the truncated apoB proteins.
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PMID:Carboxyl-terminal truncation impairs lipid recruitment by apolipoprotein B100 but does not affect secretion of the truncated apolipoprotein B-containing lipoproteins. 830 Jun 20

Studies of truncated apoB peptides in human subjects with familial hypobetalipoproteinemia, as well as of puromycin-generated spectra of nascent apoB peptides in rat and hamster liver, suggest that a minimum size is required for N-terminal fragments of apoB to be efficiently assembled into full-sized VLDL. We report here results of experiments undertaken to examine this phenomenon in greater detail by expressing individual carboxyl-truncated human apoB constructs in McArdle cells. Thus, apoB-29, -32, -37, -42, -47, -53, -70 and full length apoB-100 were transiently expressed in rat McA-RH7777 hepatoma cells, or human apoB-31 and apoB-53 were stably expressed in the same cells, and the secreted VLDL particles were characterized by kinetic gradient ultracentrifugal flotation. Calibration with rat plasma VLDL subfractions showed that about 90 and 50%, respectively, of lipoprotein particles containing endogenous rat B-100 and B-48 floated between fractions 2;-8 of the 11-fraction gradient. This corresponds to the normal VLDL diameter range of about 47 to 28 nm, with the remaining half of rat B-48 recovered as HDL particles in the 1.1 g/ml range. In contrast, regardless of their size, only 2;-5% of any of the truncated human apoB peptides expressed in these cells was recovered in the VLDL region of the gradient. The remaining 95+% of the lipoproteins were found as high density particles; as previously found in other systems the densities of the latter were inversely related to their peptide chain-length. Furthermore, transiently expressed full-length human apoB-100 was inefficiently secreted as VLDL by these cells, with the remainder appearing as LDL-sized particles. Thus, although we showed that McA-RH7777 cells secreted endogenous rat apoB as normal-sized VLDL, we found them unsuitable for our original purpose of using human apoB fragments to further define effects of apoB size on VLDL assembly. These cells appeared unable to efficiently use any size of human apoB for that process. Pulse-labeled untransfected McA-RH7777 cells chased in the presence of puromycin did, however, show a sharp decline in VLDL assembly efficiency for endogenous nascent rat apoB peptides shorter than B-48, similar to that originally found in normal rat liver.
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PMID:Rat McA-RH7777 cells efficiently assemble rat apolipoprotein B-48 or larger fragments into VLDL but not human apolipoprotein B of any size. 1062 9

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.
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PMID:Hepatitis C virus, cholesterol and lipoproteins--impact for the viral life cycle and pathogenesis of liver disease. 2369