Composition and metabolism of low-density lipoproteins in rabbits of various ages

It is shown that in old (aged 48-54 months) rabbits the percentage of low-density lipoproteins in the blood serum increases as compared to that in young (aged 6-10 months) animals. The age accumulation of the mentioned lipoproteins is combined with their slow removal from the blood. A decrease in the income of lipoproteins of the given class and their slow removal in the vascular wall of old rabbits is observed.     

Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet

Rabbits fed a cholesterol-free semi-synthetic wheat-starch-casein diet had a high plasma cholesterol concentration; most of the cholesterol was associated with low-density lipoproteins (LDL). Chemical analyses of plasma lipoproteins revealed that very-low-density lipoproteins (VLDL), intermediate lipoproteins and LDL from casein-fed rabbits contained more cholesteryl ester than that of lipoproteins isolated from chow-fed animals. The fatty acid composition of cholesteryl esters of plasma lipoproteins showed that there were higher contents of oleic acid than linoleic acids in lipoproteins from casein-fed rabbits. Lipoproteins isolated from liver perfusates of casein-fed rabbits had higher cholesteryl oleate content than lipoproteins from chow-fed rabbit liver perfusates. There was a marked increase in secretion of apolipoproteins from perfused livers of casein-fed rabbits. We conclude that the high levels of plasma cholesterol in casein-fed rabbits are of hepatic origin and that one of the hypercholesterolemic actions of dietary casein in rabbits is the induction of hepatic synthesis and secretion of cholesteryl-ester-rich lipoproteins.     

Influence of lysophosphatidylcholine on the metabolism of plasma lipoproteins.

Both low density lipoproteins and cellular membranes are known to have a high affinity for lysophosphatidylcholine. In this study lysophosphatidylcholine influenced the retention of lipoproteins by arterial tissue in vitro and the rate of disappearance of low density lipoproteins from the blood in vivo. Pieces of aorta from rabbits or rhesus monkeys were successively incubated for 90 min each in 2 or 3 solutions. After the last incubation the intima plus inner media was dissected from the remainder of the aorta for analysis. The second incubation always contained lipoproteins labeled with [3H]leucine. When lysophosphaticylcholine was included in the first but not in the second incubation fluid, the retention of low, or high density lipoproteins by the intima plus inner media increased. A subsequent incubation of the piece of artery in a fluid with trypsin or lysophosphatidylcholine caused a release of some of the lipoproteins. Lysophosphatidylcholine was bound simultaneously by plasma low density lipoproteins and vascular tissue in vitro and appeared to promote the association of the latter two components. When lysophosphatidylcholine equal to 2--10 times the usual total intravascular content was injected intravenously into control squirrel monkeys or rabbits, it was rapidly cleared from the blood. On the other hand, injected lysophosphatidylcholine persisted in the blood of hyperlipoproteinemic rabbits and was associated with the low density lipoproteins. In control animals, the injection of lysophosphatidylcholine was associated with an increase in the rate of removal of 125I-labelled low density lipoprotein from plasma and of its appearance in liver.     

Effect of aging on the response of biochemical markers in the rabbit subjected to short-term partial bladder obstruction

Purpose Partial bladder outlet obstruction (PBOO) results in marked biochemical alterations in the bladder. In this study, we focused on comparison of thapsigargin sensitive sarco/endoplasmic reticulum Ca²⁺ ATPase activity (SERCA) and Citrate Synthase after short term PBOO in young versus old rabbits. Materials and methods A total of 20 young and 20 mature male rabbits were divided into 4 sub-groups of 5 rabbits each (4 obstructed and 1 sham-control rabbit). The rabbits in the groups were evaluated after 1, 3, 7, and 14 days of obstruction, respectively. The activities of SERCA and citrate synthase were examined as markers for sarcoplasmic reticular calcium storage and release and mitochondrial function, respectively. Results The SERCA activity of bladder body smooth muscle in the young animals increased at 7 and 14 days. For the old rabbits, the SERCA activity decreased significantly by 1 day and remained this level throughout the course of obstruction, and was significantly lower than young at all time periods. The citrate synthase activity in the young animals decreased over the 1–7 days, and then returned toward control level by 14 days following obstruction. In the old animals, citrate synthase activity of bladder body smooth muscle progressively decreased over the course of the study, and was significantly lower in the old than the young animals after 14 days obstructed. Conclusion The urinary bladders of the young rabbits have a considerable greater ability to adapt to PBOO than do those of the old rabbits. The deterioration of mitochondrial and SR function may be important mechanisms underlying geriatric voiding dysfunction.     

Early changes in plasma lipoprotein structure and biosynthesis in cholesterol-fed rabbits

Plasma lipoproteins of d < 1.063 g/ml from rabbits fed a diet containing 1% cholesterol for 4 days showed changes in concentration and rates of flotation as determined by analytical ultracentrifugation. A marked increase in cholesteryl ester content of lipoprotein with d < 1.019 g/ml was the most prominent change in rabbits fed the diet for 21 days. Gel electrophoresis and immunochemical procedures demonstrated that in control and hypercholesterolemic rabbits there were some common apolipoproteins found in all lipoproteins with density < 1.063 g/ml. In control rabbits, there were also apolipoproteins specific to the lipoprotein fraction with d < 1.019 and to the fraction with d 1.019-1.063 g/ml. However, in rabbits fed the hypercholesterolemic diet for 21 days, the apolipoproteins characteristic of fraction 1.019-1.063 were the most abundant in the fraction with d < 1.019 g/ml. Liver slices from rabbits fed the high cholesterol diet for 7 and 21 days incorporated more l-[(14)C]leucine into very low density and low density lipoproteins than controls. The results suggest that cholesterol feeding leads to an increase in biosynthesis of lipoproteins with d < 1.063 g/ml. The newly synthesized lipoprotein contains apolipoproteins similar to those found in controls but with a higher lipid-to-protein ratio. From the apoprotein composition, it is concluded that the very low density fraction present in cholesterol-fed animals is more structurally related to low density lipoproteins than to the very low density lipoproteins isolated from control animals.     

The reaction of vascular endothelial cells in old animals to an increased blood level of angiotensin II

The comparative morphological investigation of endothelium (E) of femoral arteries in old and young rabbits has revealed quantitative differences in the content of cells differing in their structure and function, and a four-fold increase in the number of cells having some signs of malfunction or injury in the E of old vs. young animals. These peculiarities, as well as different initial functional state of groups of cells, their location in the intima and degree of their compression during a 30 min vasoconstriction induced by angiotensin II (0.5 microgram/kg-1.min-1) predetermine a different degree of injury of endothelial cells. A phasic response of endothelial cells to angiotensin II administration, as well as slow restoration of permeability and autolysis of part of the injured endothelial cells in old animals are revealed. A peculiar pattern of the endothelial injury in old animals at a sharp increase of the blood pressure may account for the causes of the accelerated formation of fibrous-muscular thickenings and lipid strips in arteries of old rabbit at chronic hypertension.     

Lipid peroxidation during extreme hyperthermia of rats

The influence of extremal cryoeffects on the state of prooxidant and antioxidant systems in the blood serum and heart tissues was studied in young and old rats. It is shown that kinematic parameters of chemiluminescence after cold effects are less expressed in the blood serum of old animals than in young ones. The level of TBA-active products in the blood of young rats was lower than in old ones. After the 6th and 9th cold effect the content of TBA-active products in old animal appoaches such indices in young animals. Three weeks after the cold effects the content of TBA-active products in the myocardium of old rats corresponded to control indices, while in the young ones they were considerably lower. The fermentative link state was investigated in the antioxidant protection system. After the extremal cryoeffects glutathione reductase and glutathione peroxidase activity in old animals approaches its indices in intact rats, while catalase activity increases. Three weeks after cryoeffects one can observe a stable increase of fermentative activity of heart tissues both in old and young animals compared with the control that can evidence for the increase of the organism cold resistance.     

Oxidized lipoproteins in blood plasma: possible marker of atherosclerosis progression

Oxidized lipoproteins and antioxidants were detected during the course of hypercholesterolemia development in cholesterol-fed rabbits. Lipid peroxides in blood plasma and very-low-, low-, and high-density lipoproteins (beta-VLDL, LDL, and HDL) were increased during the course of hypercholesterolemia. The content of phospholipid peroxides increased in beta-VLDL and LDL in parallel to that of cholesterol, whereas the amount of alpha-tocopherol was decreased either in lipoproteins or blood plasma. Ascorbate and urate concentrations were also decreased. Lipid peroxides were positively correlated with volume and area of atherosclerotic lesions, suggesting a relation between the concentrations of lipid peroxides in blood plasma and the progression of atheromatous lesions.     

Age-related features of protein synthesis rhythm. Effects of extracellular medium

Cell interactions have been studied in cultures pf hepatocytes from young and old rats. The rhythm of protein synthesis is an index of cell interaction and synchronization in culture, while the amplitude of oscillations characterized cell cooperation in an aggregate rhythm. The mean rhythm amplitude in the culture of hepatocytes from old rats is twice lower than that from young rats. Gangliosides (mixture, bovine brain gangliosides) and ₁-adrenomimetic phenylephrine enhanced synchronization of cultures of the cells from old rats and increased the amplitude of oscillations to the level of young animals. Addition of rat blood serum (10%) to the medium revealed the rhythm of protein synthesis in the culture, asynchronous in the control, i.e., led to their synchronization. In media with young and old rat blood sera, oscillations were intense, with high amplitudes, and low, respectively. Addition of bovine brain gangliosides to a medium with old rat blood serum increased the amplitudes of oscillations to a level of the rhythm stimulated by the young rat serum. Thus, the cells of old animals can fully perceive synchronizing factors and, in the case of their increased concentration, the rhythm of protein synthesis in old animals did not differ from that in young rats. Current data on biochemical mechanisms underlying intercellular cooperation in the formation of population rhythm of protein synthesis have been discussed.Translated from Ontogenez, Vol. 36, No. 1, 2005, pp. 9–17.Original Russian Text Copyright © 2005 by Brodsky, Nechaeva, Zvezdina, Novikova, Gvazava, Fateeva, Malchenko.     

Aging effects on the liver aldolase of rabbits (Short Communication)

A chemical method is used to determine the amount of aldolase sequence in rabbit livers. It is demonstrated that the aldolase sequences of the livers of young rabbits are more efficient catalytically than are those from the livers of old rabbits. The presence of altered residues in the aldolase sequences of old animals may account for these observations.     

Effect of hyperchylomicronemia and hyperprebetalipoproteinemia on the vascular walls of rats of different ages]

The effect of hyperchylomicronemia and hyperprebetalipo-proteinemia on the vascular wall of 6--10 and 26--30-month-old rats was studied. These animals were injected intravenously with the blood serum taken from rats, preliminarily treated with Triton WR 1339 (intraperitoneal administration). The electron microscopy study revealed the presence of inclusion of chylomicrons and lipoproteins of very low density in the endothelium of old animals only. Swelling of the Golgi complex and mitochondria, expansion of the cysterns of endoplasmic reticulum in the endothelial cells of young rats pointed to the activation of intracellular metabolic processes. The study under these conditions of the biosynthesis of some lipid classes in the aorta showed a similar inhibition of free cholesterol biosynthesis in rats of various age. An increase of phospholipid biosynthesis was recorded in young animals only.     

Ventricular myosin from young and adult animals with respect to the thyroid state

Studies were conducted to analyze the effect of the thyroid hormone on ventricular myosin during ontogenesis of mice, rats and rabbits. Hypothyroidism was induced in mice and rats by administering propylthiouracyl in drinking water. Rabbits were made hyperthyroid by chronic administration of thyroxine. The change in the thyroid state of rats and rabbits influenced young and adult animals differently depending on whether V1 or V3 was the major ventricular isomyosin form present. Measurements of Ca2+-ATPase activity of myosins from young and old control animals and from animals with changed thyroid state showed that hypothyroidism in rats is associated with a greater decrease of myosin ATPase in young rats which contain V1 isomyosin only, when compared with old rats which contain a preponderance of V3 isomyosin and less of the V1 form. In rabbits, ATPase activity of ventricular myosin was more elevated after thyroxine administration in adult rabbits, which contain V3 isomyosin only, than in young rabbits in which myosin consists of V1 and V3 isomyosins. Ventricular myosins of young and adult mice did not differ in their ATPase activity and the treatment of mice with propylthiouracyl had only slight effect on myosin ATPase. It can be concluded based on these results that the hypothesis concerning hypothyroidism inducing transformation of V1 into V3 isomyosin does not hold generally.     

Age-related features of protein synthesis rhythm in hepatocytes. Effects of extracellular medium

Cell interactions have been studied in cultures pf hepatocytes from young and old rats. The rhythm of protein synthesis is an index of cell interaction and synchronization in culture, while the amplitude of oscillations characterized cell cooperation in an aggregate rhythm. The mean rhythm amplitude in the culture of hepatocytes from old rats is twice lower than that from young rats. Gangliosides (mixture, bovine brain gangliosides) and alpha1-adrenomimetic phenylephrine enhanced synchronization of cultures of the cells from old rats and increased the amplitude of oscillations to the level of young animals. Addition of rat blood serum (10%) to the medium revealed the rhythm of protein synthesis in the culture, asynchronous in the control, i.e., led to their synchronization. In media with young and old rat blood sera, oscillations were intense, with high amplitudes, and low, respectively. Addition of bovine brain gangliosides to a medium with old rat blood serum increased the amplitudes of oscillations to a level of the rhythm stimulated by the young rat serum. Thus, the cells of old animals can fully perceive synchronizing factors and, in the case of their increased concentration, the rhythm of protein synthesis in old animals did not differ from that in young rats. Current data on biochemical mechanisms underlying intercellular cooperation in the formation of population rhythm of protein synthesis have been discussed.     

Cholagogic effect of trimethylglycine in normal animals of different ages and in experimental atherosclerosis

Trimethylglycine at a dose of 1.5 g/kg was found to produce marked bile secretory effect in young and old rats. In rabbits with experimental atherosclerosis, trimethylglycine increased the content of biliary acids in the bile and normalized the indexes of lipid metabolism in the blood serum. Apparently, the effect on cholesterol transformation into biliary acids and its excretion with the bile is one of the mechanisms of anti-atherosclerotic action of trimethylglycine.     

Evaluation of rat and rabbit sera lipoproteins in experimentally induced hyperlipidemia by analytical ultracentrifugation

Animals of various species are widely used as models with which to study atherosclerosis and the lipoprotein metabolism. The objective of this study was to investigate the lipoprotein profiles in Wistar rats and New Zealand white rabbits with experimentally induced hyperlipidemia by means of ultracentrifugation. The Schlieren curves were utilized to compare suckling and adult rat sera to determine whether aging causes alterations in lipoprotein profiles. A striking feature of the data is the high concentration of low-density lipoproteins (LDL), (>5.2 mmol/l cholesterol) in the 2-week old rat serum pool which was greatly decreased in the 3-weeks rat serum pool (<1.3 mmol/l cholesterol). Additional experiments were performed to permit a direct comparison of the amounts of lipoprotein present in rat sera in experimental hyperlipidemia post-Triton WR 1339 administration. Rapid changes in concentrations in very low-density lipoproteins (VLDL), LDL and high-density lipoproteins (HDL) were observed after Triton injection. The administration of Triton WR 1339 to fasted rats resulted in an elevation of serum cholesterol levels. Triton physically alters VLDL, rendering them refractive to the action of lipolytic enzymes in the blood and tissues, preventing or delaying their removal from the blood. Whereas the VLDL concentration was increased markedly, those of LDL and HDL were decreased at 20 h after Triton treatment. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate of LDL aliquots, to prepare radioactive-labeled lipoproteins and to study induced hyperlipidemia in rabbits. Analytical ultracentrifugation was applied to investigate the LDL flotation peaks before and after cholesterol feeding of rabbits. Modified forms of LDL were detected in the plasma of rabbits with experimentally induced atherosclerosis. ApoB-containing particles, migrating as LDL, intermediate density lipoproteins and VLDL were the most abundant lipoproteins. Gamma camera in vivo scintigraphy on rabbits with radiolabeled lipoproteins revealed visible signals corresponding to atherosclerotic plaques of the aorta and carotid arteries.     

Age-related differences in apoptosis with disuse atrophy in soleus muscle

Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 x Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant (P=0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.     

Effects of physical exercise and aging on ascorbic acid and superoxide anion levels in peritoneal macrophages from mice and guinea pigs

The relationship of physical activity and aging, two processes with a high production of oxygen-free radicals to the ascorbate and superoxide anion (O ₂ ^- ) contents of peritoneal macrophages was studied in two animal species: guinea-pig (in which ascorbic acid is a vitamin) and mouse (in which ascorbic acid is not a vitamin). The effects of exhaustive exercise were examined in young and old animals. The results show that macrophages from old animals have a lower ascorbate content than those from young ones, whereas with exercise the ascorbate content increased in both old and young animals. This increase was higher in young than in old animals, and more evident in mice than in guinea-pigs. Aging also resulted in an increase in the O ₂ ^- levels of macrophages. With exercise these levels decreased in young mice but increased in young guinea-pigs. In old animals the exhaustive exercise did not change the O ₂ ^- levels. The results suggest in general a lack of correlation between the intracellular ascorbate and O ₂ ^- levels in relation to both physical exercise and aging.Abbreviations PBS phosphate buffered saline - NBT nitroblue tetrazolium - PEC peritoneal exudate cells - PMN polymorphonuclear     

Effect of a single and fractionated gamma-irradiation on lipid content in rat blood and tissues]

Contents of lipids, character of blood plasma chemiluminescence and separate classes of lipoproteins as well as the content of the lipids of tissues under single and fractionated gamma-irradiation of rats in a dose of 3 Gr. The development of hyperlipidemia and hypercholesterolemia for four weeks after irradiation which are more expressed under a single irradiation, a decrease of total content of cholesterol and triglycerides in the heart and liver tissues to the end of the experiment 24 hour after irradiation are registered in the both groups of animals.     

Effect of chronic exposure to alcohol on the circulation of rats of different ages

Two groups each of young and old animals were fed nutritonally adequate liquid diet. One group of each served for control, while in the other one 36% of the total caloric intake was supplied by ethanol in place of part of the fat and carbohydrate. The young animals became rapidly adapted to the alcohol containing diet, while the aged animals refused to eat it even at the expense of transient hunger and thirst. Alcohol treatment resulted in body weight loss and the appearance of slight ST segment abnormalities in the ECG. Histological study of the myocardium revealed no pathological finding. Alcohol reduced the blood pressure, TPR, gut and skin fractions of the cardiac output, myocardial nutritive blood flow, and vascular resistance of the carcass in both groups, whereas it increased the relative weight of the heart. There was a greater decrease of blood pressure and a greater increase in the relative weight of the heart in the old than in young alcohol treated animals. Chronic exposure to alcohol results in a redistribution of circulation which is detrimental to cardiac function. This alcohol induced redistribution affects the cardiovascular system of old animals more severely.     

Tissue reaction of rats of different ages to xerophagia

Studies have been made on the ionic and osmotic indices of the blood, as well as on the content of water and electrolytes in different tissues of rats from 2 age groups (adult animals over 90 days and 18-24 days old ones) in the course of water deprivation within 7 days. It was demonstrated that concentration of sodium in and osmolarity of the blood plasma increased earlier and to a greater extent in young animals as compared to adult ones. In most of the tissues investigated, these changes were accompanied by the increase in the content of electrolytes and water. In the subcutaneous tissue, accumulation of cations and dehydration were observed. Adult rats exhibited mainly ion-accumulating processes in all the tissues investigated, whereas young animals showed mainly shifts in water content of the tissues.