Yutaka Kawarabayasi

The very low density lipoprotein receptor

The isolation of a cDNA highly homologous to that of the low-density lipoprotein (LDL) receptor revealed the presence of a lipoprotein receptor that specifically binds apolipoprotein-E-containing lipoproteins, including very low density lipoprotein (VLDL), intermediate-density lipoprotein, and β-migrating VLDL. This new receptor, designated VLDL receptor, consists of five domains that resemble those of the LDL receptor. The VLDL receptor mRNA is abundant in tissues performing active fatty acid metabolism, suggesting that the receptor may be responsible for the uptake of fatty acids in triglyceride-rich lipoproteins into muscle and fat cells.

The Role of the Very Low Density Lipoprotein Receptor in the Metabolism of Plasma Lipoproteins Containing ApoEa

Receptors for plasma lipoproteins play a key role both in the intracellular metabolism of lipids and in the clearance of lipoproteins from the plasma. The LDL receptor binds lipoproteins that contain apoBlOO and/or apoE, and carries them into cells. Its discovery by Goldstein and Brown has led to dramatic progress towards elucidating the mechanism of familial and dietary-induced hyperch~lesterolemia.~-~ Although the physiological role and regulation of the LDL receptor are now well understood, little is known about receptors for other lipoproteins. Several lines of evidence have suggested the presence of a distinct receptor for apoE-containing lipoproteins including chylomicron, chylomicron remnants, VLDL, and IDL. In particular, Kita eta!. demonstrated that apoE-containing chylomicrons were cleared normally in WHHL rabbits,lZ despite defects in LDL receptors. Recently we have isolated cDNA highly similar to the LDL receptor.lx Cells expressing this cDNA bound apoE-containing lipoproteins, VLDL, IDL, and P-VLDL, and internalized them via receptor-mediated endocytosis. This newly discovered receptor, designated “VLDL receptor,” consists of five domains that closely resemble the LDL receptor. VLDL receptor mRNA is abundant in heart, muscle, adipose tissue, and brain, suggesting that the receptor plays a role in the uptake of fatty acids in triglyceride-rich lipoproteins into muscle and fat cells. In this paper, we describe the structure and properties of the newly discovered receptor and discuss its possible role in lipoprotein metabolism.

Effects of Acute Hypotensive Hemorrhage on Arginine Vasopressin Gene Transcription in the Rat Brain

To determine whether hypotensive hemorrhage has an effect on arginine vasopressin (AVP) gene expression, 16 ml/kg of arterial blood was drawn over 10 min in conscious unrestrained rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured, and the rats were decapitated before and 10 min, 1, 3, 6, 9, 12, and 24 h after the initiation of hemorrhage. The hypothalamic or cerebro-hypothalamic tissue was used to measure AVP mRNA by Northern blot analysis, and the trunk blood to measure plasma AVP, osmolality and hematocrit. Hemorrhage brought about rapid and transient decreases in MABP and HR accompanied by transient increases in plasma osmolality and AVP. Hematocrit decreased after the bleeding and reached a stable level 6 h after hemorrhage and thereafter. AVP mRNA was detected in the hypothalamus and not in the extrahypothalamic cerebral brain tissue under basal and posthemorrhage conditions. AVP mRNA in the cerebro-hypothalamic tissue increased by 1.8-fold at 6 h and 2.1-fold at 9 h after hemorrhage. These results indicate that AVP mRNA in the brain increases 6 h after increased AVP release in response to hypotensive hemorrhage.

Human Granulocyte‐Macrophage Colony‐Stimulating Factor Lowers the Levels of Plasma Cholesterol with an Increase in mRNA for Very Low Density Lipoprotein Receptor in Rabbitsa

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation of progenitor cells in the granulocyte-macrophage lineage and stimulates the function of the mature cells. It has been shown that the levels of cholesterol are reduced by the administration of macrophage colony-stimulating factor (M-CSF) or GM-CSF to animals and humans.- The mechanisms by which M-CSF lowers plasma cholesterol levels have been extensively However, little is known about the effects of GM-CSF on cholesterol homeostasis and its mechanism(s). We tested the ability of human GM-CSF on lipid metabolism in rabbits and attempted to determine the mechanism(s) of the cholesterol-lowering effect. Twenty pg/kg per day of human GM-CSF was administered subcutaneously to normal and cholesterol-fed rabbits daily in two divided doses for 12 days. An equal dose of human serum albumin (HSA) served as control. The administration of human GM-CSF markedly lowered the levels of plasma cholesterol and triglycerides (n = 6), whereas HSA produced no significant changes in plasma lipid content (n = 9). The levels of total cholesterol were decreased by 51 2 19% (mean ? SD) of pretreatment values ( p < 0.01) with a 47 * 27% decrease in triglycerides ( p < 0.01) in the normal rabbits. The reduction in plasma cholesterol was primarily attributed to a marked lowering of both low-density lipoprotein (LDL) and very-low-density

GENOTYPE ANALYSIS OF PREPRO-VASOPRESSIN SIGNAL PEPTIDE IN VASOPRESSIN-PRODUCING AND -NON-PRODUCING LUNG TUMORS

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.