Apolipoprotein E (apoE) has a high affinity to cell-surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma lipoprotein metabolism, transgenic mouse lines with integrated rat apoE gene under the control of the metallothionein promoter were established. We found that a high expresser line produced rat apoE mainly in the liver, and the gene product was almost entirely assodated with plasma lipoproteins. The plasma level of rat apoE in homozygotes for the transgene was 17.4 mg/dl after zinc induction (vs. 4.56 mg/dl of mouse apoE in controls). In this group, plasma cholesterol and triglyceride levels were 43% and 68% reduced as compared with controls, respectively. Heterozygotes showed decreases in both lipids to a lesser extent. Gel filtration chromatography showed that lipid reduction was mainly due to decreased very low density lipoproteins (VLDL) and LDL. Especially in zinc-treated homozygotes, VLDL had almost disappeared, and a remarkable decrease in LDL and a slight decrease in high density lipoprotein were also observed. Consistently, the plasma level of apoB, a structural protein of VLDL and LDL, was 78% lower than that of controls, indicating a marked reduction in lipoproteins containing apoB. Furthermore, the transgenic mice, in contrast to controls, did not develop hypercholesterolemia when fed a high cholesterol diet. These results demonstrated that overexpression of apoE reduces plasma cholesterol and triglyceride levels and prevents diet-induced hypercholesterolemia. From dramatic and doserelated decreases in plasma lipoproteins in transgenic mice, we conclude that apoE plays a key role in plasma lipoprotein metabolism.Apolipoprotein E (apoE) is a major component ofmammalian lipoproteins along with apolipoprotein B100 (apoB100) and functions in metabolism of plasma lipoproteins through its interaction with the low density lipoprotein (LDL) receptor mainly in the liver (for a review, see ref. 1); apoE is also thought to be a specific ligand for the putative hepatic chylomicron remnant receptor (apoE receptor) (1). Expressed in many tissues, apoE plays a crucial role in transport and redistribution of lipids in peripheral tissues such as brain, peripheral nerve, and arterial wall (1). Several lines of evidence suggest that lipoproteins with several molecules of apoE have a higher affinity for LDL receptors than those without apoE (1-7). In vitro studies have shown that enrichment in apoE on very low density lipoprotein (VLDL) particles increases uptake of these lipoproteins both when cells were cultured with human VLDL that had been incubated with excess purified apoE or recombinant apoE (3,8,9) and when the transfected CHO cells overexpressing apoE were cultured with unmodified human VLDL (10). Recently, we and another group have reported that intravenous administration ofapoE causes the incorporation ofexogenous apoE onto plasma lipoproteins, enhances clearance of VLDL, and reduces the production of LDL from VLDL, resulting in a lowered plasma cholesterol l...
Volume 37, no. 2, p. 148, Table 3: Growth at 40°C should read " + " for P. avenue and P. cattleyae.
During seed embryogenesis, glycinin, the 11-S seed storage protein found in soybeans, undergoes post-translational proteolytic processing, in which a proprotein molecule is cleaved into an acidic and a basic subunit by a one-point cleavage that occurs at the carboxyl side of the asparaginyl residue located at the junction of the subunits. To elucidate the mechanism of this very limited proteolysis, we purified the cysteine endoprotease and used purified proglycinin produced by Escherichia coli as a substrate. This enzyme was separated by isoelectric focusing into three isomeric forms: two had a molecular mass of 33 kDa and the third, 33.8 kDa. The cysteine protease was found both in the proteinaceous vacuoles of cotyledonary tissue of immature seeds and in mature seeds, and is the first proteolytic enzyme to be classified as an asparagine-specific endoprotease. The results also indicate that the above proteolysis is largely attributable to the conformational accessibility of the enzyme to the asparaginyl residue in the cleavage site of proglycinin. The conformation of this single enzyme-accessible region on the proglycinin molecule is relatively flexible and becomes unstable under low salt conditions, or when heat is applied, causing the enzyme to lose its specificity.Many proteins are biosynthesized in the prepro-type form, whereby another selective proteolytic cleavage occurs post-translationally in addition to co-translational processing, and this is catalyzed by a variety of different enzymes (Neurath, 1986). In general this proteolytic conversion, either as a single step or a cascade, allows a conformational change in the inactive proprotein to take place, producing a physiologically active form. This second processing step is of importance during 'maturation' and is closely related to the regulation of biological systems (Neurath and Walsh, 1976).The 11-S seed storage protein family which is prevalent in seed plants (Derbyshire et al., 1976) and functions as a reserve of nitrogen and carbon during seedling growth, also undergoes this post-translational proteolysis. In the case of soybean [Glycine max (L.)] seeds, glycinin, which is the trivial name of the 11-S storage protein, is synthesized as the subunit precursor on the rough endoplasmic reticulum of cotyledonary parenchyma cells during embryogenesis. The preproglycinin subunit is cleaved co-translationally to remove the signal peptide region; the resulting proglycinin subunits
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