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H Shimano

Publications and source records attributed to H Shimano.

101 records · Page 6Linked to original sources
PubMed1989

Increased clearance of plasma cholesterol after injection of apolipoprotein E into Watanabe heritable hyperlipidemic rabbits.

Apolipoprotein E (apoE) is known to play an important role in lipoprotein metabolism. We have studied the effect of apoE on the metabolism of plasma cholesterol by injecting apoE intravenously into rabbits deficient in low density lipoprotein receptors [Watanabe heritable hyperlipidemic (WHHL) rabbits]. Approximately 30 mg of apoE was injected per rabbit; a total of five WHHL rabbits were used. One hour later, plasma cholesterol levels fell 8.3% (from 488 +/- 192 to 446 +/- 174 mg/dl). After 3 hr, cholesterol levels had fallen by 19% (to 392 +/- 152 mg/dl). The reduced levels were maintained for at least 8 hr after injection of apoE. Cholesterol in very low density lipoproteins (VLDLs) and intermediate density lipoproteins fell rapidly during the first 2 hr after injection, followed by a reduction in the low density lipoprotein cholesterol level. Changes in apolipoprotein B levels in each lipoprotein fraction were very similar to those of cholesterol. Plasma apoE levels 3 min after injection were elevated 3-fold to 22.8 +/- 6.3 mg/dl and returned to initial levels 8 hr after injection. The rate of removal of intravenously injected 125I-labeled VLDL that had been incubated with apoE was 3-fold higher than that of unmodified VLDL. From these results, we conclude that the injected apoE is incorporated into VLDLs and that VLDL particles carrying more apoE are removed from the blood more rapidly, resulting in reduced formation of low density lipoprotein and lowered cholesterol levels.

Animals↗
PubMed1989

Composition of very-low-density lipoproteins in non-insulin-dependent diabetes mellitus.

We studied the characteristics of very-low-density lipoproteins (VLDLs) composition in patients with non-insulin-dependent diabetes mellitus. VLDLs were isolated from 28 diabetics and 33 nondiabetics with a wide range of plasma lipid concentrations, so we could compare VLDL composition between the two groups at similar lipid concentrations. The mean cholesterol and triglyceride concentrations in plasma of diabetic subjects were 2170 (SD 570) and 2510 (SD 2230) mg/L, respectively, and 2230 (SD 560) and 2210 (SD 1830) mg/L in nondiabetics. Diabetic subjects showed positive correlations between plasma triglyceride concentrations and either preprandial blood glucose or glycated hemoglobin values (P less than 0.02 and less than 0.01, respectively). Concentrations of triglycerides, cholesterol, and apolipoproteins (apo) B, CII, CIII, and E in VLDL were not significantly different between diabetics and nondiabetics. At comparable triglyceride concentrations, the chemical compositions of the VLDL in the two groups were still very similar. Dividing the concentration of each component by the VLDL-apo B concentrations yielded similar contents of each component per unit of VLDL for the two groups. We conclude that the composition of VLDLs in diabetics is much the same as that in nondiabetics at comparable concentrations of triglycerides in plasma.

Adult↗
PubMed1988

Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury.

To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with [35S]methionine. The [35S]labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy.

Animals↗
PubMed1988

Down-regulation of hepatic LDL receptor protein and messenger RNA in fasted rabbits.

Rabbits fasted for 9 and 14 d exhibited 6- and 8-fold increase in plasma cholesterol level, respectively. As one of the mechanisms causing hypercholesterolemia in fasted rabbits, the decreased activity of hepatic low-density lipoproteins (LDL) receptor has been reported (Stoudemire, J.B., Renaud, G., Shames, D.M., & Havel, R.J. (1984) J. Lipid Res. 25, 33-39). In order to demonstrate the down-regulation of hepatic LDL receptor on a molecular basis, we carried out immunoblotting of the liver membranes with a specific antibody against LDL receptors and blot hybridization of hepatic RNAs with cDNA of LDL receptor. Immunoblotting showed that LDL receptors in fasted rabbits were markedly decreased, and blot hybridization of RNAs showed a significant decrease in mRNA level of hepatic LDL receptor in fasted rabbits. Further, significant decreases both in LDL binding to liver membrane and in hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in fasted rabbits were demonstrated. From these results, we concluded that hypercholesterolemia in fasted rabbits is caused by the impaired catabolism of LDL due to down-regulated biosynthesis of hepatic LDL receptor.

Animals↗
PubMed1987

High-cholesterol diet-induced lipoproteins stimulate lipoprotein lipase secretion in cultured rat alveolar macrophages.

We have previously shown that cultured rat alveolar macrophages synthesize and secrete lipoprotein lipase into the medium. The purpose of the present experiments is to examine whether cholesterol-enriched lipoproteins from cholesterol-fed animals have any effects on the lipoprotein lipase secretion and the lipid accumulation in macrophages. Macrophages incubated with the VLDL obtained from rats fed a normal diet secreted 2-fold higher amounts of lipoprotein lipase than those without lipoproteins. Intermediate-, low- and very-low-density lipoproteins from rats fed a high-cholesterol diet also enhanced the lipoprotein lipase secretion. Normal high- and low-density lipoproteins, and high-density lipoproteins from hypercholesterolemic animals did not cause any increase in the lipoprotein lipase secretion. The lipoproteins which stimulated the lipoprotein lipase secretion caused intracellular accumulation of both triacylglycerol and cholesterol. It is speculated that macrophages residing in the environment rich in lipoproteins, especially hypercholesterolemic lipoproteins, take them up and accumulate lipids intracellularly, and that this process links with the lipoprotein lipase secretion. The secreted lipoprotein lipase could facilitate, by degrading lipoproteins, the uptake of lipoprotein lipase-modified lipoproteins. Probably such a series of events is of importance in the foam cell formation of macrophages.

Animals↗
PubMedDate not supplied

Overexpression of low density lipoprotein receptor on Chinese hamster ovary cells generates foam cells.

The atherosclerotic lesion is characterized by the presence of cholesterol-loaded foam cells. Chinese hamster ovary (CHO) cells do not normally store cholesteryl esters because low density lipoprotein (LDL) receptors are suppressed by exposure of these cells to LDL cholesterol. We transfected LDL receptor cDNA linked to the simian virus 40 early promoter into CHO cells (CHO 29) and found that LDL receptor binding in these cells was not suppressed by an excess amount of LDL cholesterol, indicating no regulation of the LDL receptor in CHO 29 cells. Furthermore, CHO 29 cells showed a high activity of LDL uptake and intracellular accumulation of cholesteryl esters. Light-microscopic examination demonstrated the resulting formation of foam cells in CHO 29 cells in the presence of 5 micrograms LDL/ml. These results demonstrated that foam cell changes in atherosclerotic lesions can be reproduced in CHO cells, whose LDL receptor activity is overexpressed, through the mechanism of LDL receptor-mediated endocytosis of native LDL.

Animals↗
PubMedDate not supplied

Effects of human recombinant macrophage colony-stimulating factor on the secretion of lipoprotein lipase from macrophages.

The effects of human recombinant macrophage colony-stimulating factor (M-CSF) on the secretion of lipoprotein lipase were studied in rat alveolar macrophages. Five nanograms per milliliter M-CSF significantly enhanced lipoprotein lipase secretion (threefold), and the maximal effect (10-fold) of M-CSF on lipoprotein lipase secretion was observed at a dose of 200 ng/ml M-CSF. The effect of M-CSF was time dependent but was not manifested during the first 8 hours of incubation. After 24 hours, its effects were evident and dose dependent. On blot hybridization of macrophage RNAs with human cDNA of lipoprotein lipase, a remarkable and dose-dependent increase in mRNA level (7.3-fold) was found in M-CSF-treated alveolar macrophages. The secretion of lipoprotein lipase was also enhanced in human monocyte-derived macrophages (2.6-fold), whereas the secretion from either THP-1 cells, P388 cells, or J774 cells was not significantly enhanced. These results indicate that the stimulation of lipoprotein lipase secretion after M-CSF treatment was evident in rat alveolar macrophages and human monocyte-derived macrophages on the basis of both enzyme activity and mRNA level; therefore, M-CSF may be involved in lipoprotein metabolism of macrophages through modulation of the secretion of lipoprotein lipase.

Animals↗
PubMedDate not supplied

Enhanced lipoprotein lipase secretion from human monocyte-derived macrophages caused by hypertriglyceridemic very low density lipoproteins.

We studied the effects of very low density lipoprotein (VDL) obtained from hypertriglyceridemic subjects on the secretion of lipoprotein lipase and lipid accumulation in human monocyte-derived macrophages. The incubation of macrophages with VLDL obtained from different subjects caused different effects on the secretion of lipoprotein lipase (6.8 to 137.7 nM free fatty acid/min/mg cell protein) and triglyceride accumulation (184 to 507 micrograms/mg cell protein) in human monocyte-derived macrophages. VLDL from subjects with marked hypertriglyceridemia (approximately 1000 mg/dl) had a fourfold greater effect on lipoprotein lipase activity and a twofold greater effect on cellular triglyceride accumulation when compared with the effects of VLDL from normolipidemic subjects. Both lipoprotein lipase activity and triglyceride accumulation correlated positively with plasma VLDL triglyceride levels (r = 0.50 and 0.45, respectively, p less than 0.05). From these data, we suggest that the activity of lipoprotein lipase secreted from macrophages incubated with VLDL was dependent on triglyceride concentrations, and that the secretion of lipoprotein lipase enhanced by hypertriglyceridemic VLDL was closely related to the intracellular accumulation of triglyceride.

Cell Line↗