Relationship between exercise-induced changes in serum and hepatic cholesterol metabolism in rats

The purpose of the present study was to determine the effects of exercise training on serum cholesterol level and hepatic cholesterol metabolism in rats. Twenty-four male Wistar strain rats, aged 6 weeks, were assigned to one of three experimental groups; control (n = 8), exercised 20 minutes a day (E20, n = 8), and exercised 60 minutes a day (E60, n = 8). Rats were sacrificed after ten weeks exercise. The levels of serum total cholesterol and HDL-cholesterol in the group E20 and group E60 were lower than that of control, 8% and 24% (p less than 0.01) for the total cholesterol and 10% and 24% (p less than 0.05) for the HDL-cholesterol, respectively. The activity of HMG-CoA reductase in liver microsome was significantly higher in the group E60 than that of control. The hepatic microsomal HMG-CoA reductase activity was negatively related to serum total (r = -0.62, p less than 0.01) and HDL (r = -0.58, p less than 0.01) cholesterol levels. From these results, we concluded that the enhancement of the cholesterol metabolism in the liver by exercise is a major course of the exercise-induced change in serum cholesterol of Wistar rats.     

Haemoglobin metabolism in mice with a hereditary iron deficiency anaemia (sla/Y)

• 1.1. Haemoglobin was labelled in vivo in normal mice and in mice with iron deficiency anaemia due to the X-linked gene mutation, sla.
• 2.2. Two main red cell populations are found in normal mice, one subject to accelerated destruction and the second with a longer finite life span.
• 3.3. In iron deficient sla / Y mice, haem and globin labelling indicate random haemolysis and shortened red cell survival.
• 4.4. Specific activity curves of faecal urobilinogen show complex “early” labelling patterns. They confirm mean red cell survival in both normal and anaemic mice. and indicate increased ineffective erythropoiesis in the sla/Y animals with iron deficiency.

     

Competition affects gene flow from oilseed rape (female symbol) to Brassica rapa (male symbol)

Unlike most studies on hybridisation between oilseed rape and Brassica rapa, this study focused on hybridisation with oilseed rape as the maternal parent. This is a key cross because, assuming that plastids are inherited maternally, F(1)-hybrid production with maternal oilseed rape (B. napus) is the only transgene escape route from transplastomic oilseed rape. We investigated such F(1)-hybrid production in winter oilseed rape co-cultivated with weedy B. rapa at three plant densities each with two proportions of the different species. The paternity of the progeny produced on oilseed rape was assessed, and several fitness parameters were determined in oilseed rape mother plants in order to correlate hybridisation and plant competition. At higher density, the vegetative fitness per mother plant decreased significantly, but the density only affected the frequency of F(1)-hybrids significantly (a decrease) in the treatment with equal proportions of each species. As to the proportions, at higher B. napus frequencies, there were fewer F(1)-hybrids per mother plant and a significant increase in most biomass components. Thus, B. rapa was the stronger competitor in its effect on both the vegetative and reproductive fitness in B. napus, and the hybridisation frequency. In conclusion, the relative frequency of the two species was a more influential parameter than the density. Hybridisation with B. napus as the female will be most likely at current field densities of B. napus and when B. rapa is an abundant weed.     

Relationship of high density lipoprotein cholesterol to cholesterol metabolism in the baboon (Papio sp.)

Genetic effects on serum high density lipoprotein (HDL) cholesterol concentration and several parameters of a two-pool model of cholesterol metabolism were investigated in 79 baboons, the progeny of 6 sires. Significant differences (P less than 0.05) were observed among the sire progeny groups for HDL cholesterol (HDL-C), cholesterol production rate, cholesterol mass of pool A, and the rate constants KA and KAB. Rank correlations (rs) revealed that the sire progeny group means for HDL-C are closely correlated with those for the cholesterol mass of pool A (rs = 0.89), KA (rs = -0.78), and KAB (rs = -0.94). These strong correlations suggest that pool A, KA, and KAB are influenced to a large degree by the same genes that regulate HDL-C concentration. The strong inverse relationship (rs = -0.78) between HDL-C and KA suggests that the differences among these sire progeny groups for HDL-C are due chiefly to those metabolic processes which regulate cholesterol excretion from pool A. This conclusion is consistent with reports that HDL-C is a preferred precursor for bile acid synthesis.     

Comparison of the metabolism of cholesterol, cholestanol, and -sitosterol in L-cell mouse fibroblasts

The following data have been obtained from comparative studies on the metabolism of cholesterol, cholestanol, and beta-sitosterol by L-cell mouse fibroblasts. (1) When the sterols are added to the growth medium under similar conditions, cellular incorporation of cholesterol > cholestanol > beta-sitosterol; (2) only limited cellular esterification of these compounds occurs; (3) no metabolic products arising from the sterols could be detected; (4) influx of all sterols is dependent upon the concentration; and (5) exogenous cholesterol reduces mevalonate incorporation into cellular sterol to a lesser extent than acetate or glucose. The metabolism of these sterols is discussed in relation to their ability to influence de novo sterol biosynthesis.     

Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse

Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe(-/-)) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe(-/-) compared to apoe(+/+) mice. Relative to apoe(+/+) mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe(-/-) and apoe(+/+) mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.     

Mitochondrial cholesterol: a connection between caveolin, metabolism, and disease

Caveolin (CAV) is an essential component of caveolae, cholesterol-enriched invaginations of the plasma membrane of most mammalian cells. However, CAV is not restricted to plasma membrane caveolae, and pools of CAV are present in myriad intracellular membranes. CAV proteins tightly bind cholesterol and contribute to regulation of cholesterol fluxes and distributions within cells. In this context, we recently showed that CAV1 regulates the poorly understood process controlling mitochondrial cholesterol levels. Cholesterol accumulates in mitochondrial membranes in the absence of CAV1, promoting the organelle's dysfunction with important metabolic consequences for cells and animals. In this article, we suggest a working hypothesis that addresses the role of CAV1 within the homeostatic network that regulates the influx/efflux of mitochondrial cholesterol.     

Genetic connections between neurological disorders and cholesterol metabolism

Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington''s disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally associated with disturbances in cholesterol metabolism, and presence of the E4 isoform of the cholesterol transporter apolipoprotein E as well as hypercholesterolemia are important risk factors for development of Alzheimer''s disease. In the present review, we discuss the links between genetic disturbances in cholesterol metabolism and the above neurological disorders.     

Relationship between cholesterol trafficking and signaling in rafts and caveolae

Caveolae and lipid rafts are two distinct populations of free cholesterol, sphingolipid (FC/SPH)-rich cell surface microdomains. They differ in stability, shape, and the presence or absence of caveolin (present in caveolae) or GPI-anchored proteins (enriched in lipid rafts). In primary cells, caveolae and rafts support the assembly of different signaling complexes, though signal transduction from both is strongly dependent on the presence of FC. It was initially thought that FC promoted the formation of inactive reservoirs of signaling proteins. Recent data supports the concept of a more dynamic role for FC in caveolae and probably, also lipid rafts. It is more likely that the FC content of these domains is actively modulated as protein complexes are formed and, following signal transduction, disassembled. In transformed cell lines with few caveolae, little caveolin and a preponderance of rafts, complexes normally assembled on caveolae may function in rafts, albeit with altered kinetics. However, caveolae and lipid rafts appear not to be interconvertible. The presence of non-caveolar pools of caveolin in recycling endosomes (RE), the trans-Golgi network (TGN) and in mobile chaperone complexes is now recognized. A role in the uptake of microorganisms by cells ascribed to caveolae now seems more likely to be mediated by cell surface rafts.     

Relationship between energy metabolism and growth

Summary A biphasic dependence of the exponential growth rate on the glucose concentration of the medium was observed in batch culture experiments for a strain of S. cerevisiae and one of its petit mutants. The data can be fitted to an equation of the Michaelis-Menten type with two sets of values of the growth parameters; the switch-over occurs at a glucose concentration of 4 mM. Another petit mutant did not show the biphasic character.Regulation of the energy metabolism in relation to the cell cycle is discussed. It is suggested that the observed shift in the growth parameters may be due to a change in the control point of glycolysis from phosphofructokinase to pyruvate kinase at higher glucose concentrations. This could reduce the duration of the G₁ phase by permitting a faster synthesis of reserve carbohydrates required as intracellular energy reservoirs for DNA synthesis.Nonstandard Abbreviations Used F6P fructose-6-phosphate - FDP fructose-1,6-diphosphate - G1P glucose-6-phosphate - PEP Phosphoenolpyruvate - PYR pyruvate Enzymes PFK phosphofructokinase (EC 2.7.1.11) - PK phosphoenolpyruvate kinase (EC 2.7.1.40)     

Relationship between cholesterol trafficking and signaling in rafts and caveolae

Caveolae and lipid rafts are two distinct populations of free cholesterol, sphingolipid (FC/SPH)-rich cell surface microdomains. They differ in stability, shape, and the presence or absence of caveolin (present in caveolae) or GPI-anchored proteins (enriched in lipid rafts). In primary cells, caveolae and rafts support the assembly of different signaling complexes, though signal transduction from both is strongly dependent on the presence of FC. It was initially thought that FC promoted the formation of inactive reservoirs of signaling proteins. Recent data supports the concept of a more dynamic role for FC in caveolae and probably, also lipid rafts. It is more likely that the FC content of these domains is actively modulated as protein complexes are formed and, following signal transduction, disassembled. In transformed cell lines with few caveolae, little caveolin and a preponderance of rafts, complexes normally assembled on caveolae may function in rafts, albeit with altered kinetics. However, caveolae and lipid rafts appear not to be interconvertible. The presence of non-caveolar pools of caveolin in recycling endosomes (RE), the trans-Golgi network (TGN) and in mobile chaperone complexes is now recognized. A role in the uptake of microorganisms by cells ascribed to caveolae now seems more likely to be mediated by cell surface rafts.     

Modeling cholesterol metabolism by gene expression profiling in the hippocampus

An important part of the challenge of building models of biochemical reactions is determining reaction rate constants that transform substrates into products. We present a method to derive enzymatic kinetic values from mRNA expression levels for modeling biological networks without requiring further tuning. The core metabolic reactions of cholesterol in the brain, particularly in the hippocampus, were simulated. To build the model the baseline mRNA expression levels of genes involved in cholesterol metabolism were obtained from the Allen Mouse Brain Atlas. The model is capable of replicating the trends of relative cholesterol levels in Alzheimer's and Huntington's diseases; and reliably simulated SLOS, desmosterolosis, and Dhcr14/Lbr knockout studies. A sensitivity analysis correctly uncovers the Hmgcr, Idi2 and Fdft1 sites that regulate cholesterol homeostasis. Overall, our model and methodology can be used to pinpoint key reactions, which, upon manipulation, may predict altered cholesterol levels and reveal insights into potential drug therapy targets under diseased conditions.     

Relationship between avirulence gene (avrA) diversity in Ralstonia solanacearum and bacterial wilt incidence

Bacterial wilt, caused by Ralstonia solanacearum, is a serious disease of tobacco in North and South Carolina. In contrast, the disease rarely occurs on tobacco in Georgia and Florida, although bacterial wilt is a common problem on tomato. We investigated whether this difference in disease incidence could be explained by qualitative characteristics of avirulence gene avrA in the R. solanacearum population in the southeastern United States. Sequence analysis established that wild-type avrA has a 792-bp open reading frame. Polymerase chain reaction (PCR) amplification of avrA from 139 R. solanacearum strains generated either 792-bp or approximately 960-bp DNA fragments. Strains that elicited a hypersensitive reaction (HR) on tobacco contained the 792-bp allele, and were pathogenic on tomato and avirulent on tobacco. All HR-negative strains generated a approximately 960-bp DNA fragment, and wilted both tomato and tobacco. The DNA sequence of avrA in six HR-negative strains revealed the presence of one of two putative miniature inverted-repeat transposable elements (MITEs): a 152-bp MITE between nucleotides 542 and 543, or a 170-bp MITE between nucleotides 461 and 462 or 574 and 575. Southern analysis suggested that the 170-bp MITE is unique to strains from the southeastern United States and the Caribbean. Mutated avrA alleles were present in strains from 96 and 75% of North and South Carolina sites, respectively, and only in 13 and 0% of the sites in Georgia and Florida, respectively. Introduction of the wildtype allele on a plasmid into four HR-negative strains reduced their virulence on both tobacco and tomato. Inactivation of avrA in an HR-positive, avirulent strain, resulted in a mutant that was weakly virulent on tobacco. Thus, the incidence of bacterial wilt of tobacco in the southeastern United States is partially explained by which avrA allele dominates the local R. solanacearum population.     

Relationship between dietary tyrosine and plasma cholesterol in the rat

The present study was undertaken to measure the effects of dietary tyrosine added to fish protein and peanut meal on plasma cholesterol and plasma thyroid hormone levels in the rat. These dietary proteins were chosen because they contain similar amounts of tyrosine but release it at different rates during enzymatic hydrolysis. Casein was chosen as the reference protein. Supplementation was used to obtain tyrosine levels similar to that of casein. Male Sprague-Dawley rats were fed cholesterol-enriched diets containing 15% protein. After 3 weeks of experimental feeding, total postprandial plasma cholesterol was similar in the casein and peanut meal groups and significantly lower in the fish group. When added to the fish diet, tyrosine caused an increase in plasma cholesterol to a level similar to that of the casein group, whereas supplementation had no effect on plasma cholesterol of rats fed the peanut meal diet. The effects of dietary proteins or of tyrosine supplementation on cholesterol levels of the (density less than 1.006 g/mL) lipoprotein fraction were comparable, but not all significant, to those observed on total plasma cholesterol. In addition, casein and fish diets induced significantly higher levels of plasma triiodothyronine (T3) and lower levels of plasma thyroxine (T4) than did the peanut meal diet. However, the addition of tyrosine to the fish or the peanut meal diet did not modify the plasma thyroid hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions between metabolism and intracellular distribution of cholesterol and sphingomyelin

There is ample evidence from experimental models and human metabolic disorders indicating that cholesterol and sphingomyelin (SM) levels are coordinately regulated. Generally it has been observed that altering the cellular content of sphingomyelin or cholesterol results in corresponding changes in mass and/or synthesis of the other lipid. In the case of cholesterol synthesis and trafficking, SM regulates the capacity of membranes to absorb cholesterol and thereby controls sterol flux between the plasma membrane and regulatory pathways in the endoplasmic reticulum. This relationship exemplifies the importance of cholesterol/sphingolipid-rich domains in cholesterol homeostasis, as well as other aspects of cell signaling and transport. Evidence for regulation of sphingomyelin metabolism by cholesterol is less convincing and dependent on the model system under study. Sphingomyelin biosynthetic rates are not dramatically affected by alterations in cholesterol balance suggesting that sphingomyelin or its metabolites serve other indispensable functions in the cell. A notable exception is the robust and specific regulation of both SM and cholesterol synthesis by 25-hydroxycholesterol. This finding is reviewed in the context of the role of oxysterol binding protein and its putative role in cholesterol and SM trafficking between the plasma membrane and Golgi apparatus.