0000000000054106
AUTHOR
Teresa Barber
Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung. Partial reversibility by retinoic acid
Vitamin A is essential for lung development and pulmonary cell differentiation. Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances. Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form. This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all-trans-retinoic acid. Male weanling pups were fed a retinol-adequate/-deficient diet …
Hepatic amino acid uptake is decreased in lactating rats. In vivo and in vitro studies.
To study the redistribution of amino acids to the mammary gland during lactation we used lactating and virgin rats fed liquid diets. Virgin rats were divided in two groups: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats), and the other virgin group was fed the normal liquid diet (control). The hepatic availability of amino acids was significantly higher in the lactating rats than in the other two groups, but the uptake and fractional extraction of amino acids by the liver were lower in lactating rats than in the high protein-fed virgin controls. When primary hepatocyte cultures were used, …
Role of Vitamin A in Mammary Gland Development and Lactation
Vitamin A (all-trans-retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. …
Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes
Whole-blood free amino acids were measured in a control group made up of eight healthy women fasted for 12 h and also in eight patients with acute pancreatitis, five patients with acute cholecystitis and seven patients with acute appendicitis. Blood was withdrawn immediately on admission to hospital and again 3 d later following a controlled peripheral parenteral nutrition diet; this is with the exception of the appendicitis group. L-CYSTATHIONINE AND l-methionine concentrations were significantly higher in pancreatitis and appendicitis patients when compared with controls. In the pancreatitis and cholecystitis patients, l-serine concentration was also significantly higher when compared wit…
In vivo studies of altered expression patterns of p53 and proliferative control genes in chronic vitamin A deficiency and hypervitaminosis
Several clinical trials have revealed that individuals who were given beta-carotene and vitamin A did not have a reduced risk of cancer compared to those given placebo; rather, vitamin A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S. & Hammar, S. N. Engl. J. Med (1996) 334, 1150-1155; Hennekens, C.H., Buring, J.E., Manson, J.E., Stampfer, M., Rosner, B., Cook, N.R., Belanger, C., LaMotte, F., Gaziano, J.M., Ridker, P.M., Willet, W. & Peto, R. (1996) N. Engl. J. Med. 334, 1145-1149]. Using differential display techniq…
Effects of vitamin A deficiency on mitochondrial function in rat liver and heart.
The aim of this study was to investigate comparative effects of vitamin A deficiency on respiratory activity and structural integrity in liver and heart mitochondria. Male rats were fed a liquid control diet (control rats) or a liquid vitamin A-deficient diet (vitamin A-deficient rats) for 50 days. One group of vitamin-A deficient rats was refed a control diet for 15 days (vitamin A-recovered rats). To assess the respiratory function of mitochondria the contents of coenzyme Q (ubiquinone, CoQ), cytochrome c and the activities of the whole electron transport chain and of each of its respiratory complexes were evaluated. Chronic vitamin A deficiency promoted a significant increase in the endo…
Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.
Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored i…
Vitamin E deficiency induces liver nuclear factor-κB DNA-binding activity and changes in related genes
The biological functions of vitamin E have been classically attributed to its property as a potent inhibitor of lipid peroxidation in cellular membranes. However, in 1991, Azzi's group first described that alpha-tocopherol inhibits smooth muscle cell proliferation in a protein kinase C (PKC)-dependent way, demonstrating a non-antioxidant cell signalling function for vitamin E. More recently, the capacity of alpha-tocopherol to modulate gene expression with the implication of different transcription factors, beyond its antioxidant properties, has also been established. This study was to determine the effect of vitamin E-deficiency on liver nuclear factor-kappa B (NF-kappaB) DNA-binding activ…
Inhibition of liver trans-sulphuration pathway by propargylglycine mimics gene expression changes found in the mammary gland of weaned lactating rats: role of glutathione
In the lactatingmammary gland, weaning produces mitochondrial cytochrome c release and nuclear DNA fragmentation, as determined by gel electrophoresis. This is followed by a significant decrease in lactation. Weaning for 2 h produces an early induction of the tumour suppressor/transcription factor p53, whereas the oncoprotein c-Jun and c-Jun N-terminal kinase are elevated after 24 h of weaning when compared with controls. The expression of p21cip1 and p27kip1, cyclin-dependent kinase inhibitors, was significantly higher in weaned rats when compared with control lactating rats. All the changes mentioned above also happen in the lactatingmammary gland when propargylglycine, an inhibitor of th…
The L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2): expression and regulation in rat lactating mammary gland.
The Na(+)-dependent L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2), were expressed in rat lactating mammary gland, but EAAC1 (EAAT3) was not. GLT-1 expression in rat lactating mammary gland was constant in all the physiological situations studied; however, the GLAST expression is under tight regulation. Fasting for 24 h decreased the GLAST expression which returned to control values after refeeding. Weaning for 24 h produced a decrease in GLAST expression through a mechanism independent of prolactin deficiency. Resuckling for 6 h returned the expression of this transporter to control values. There is a correlation between the levels of GLAST (mRNA and protein) and the in vivo upta…
Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats.
To study the fate ofl-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC4.4.1.1) activity was undetectable,l-cystathionine levels were significantly higher,l-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle,l-ornithine,l-citrulline andl-arginine and blood urea were significantly greater. Urea excretion was also higher in PPG-treated rats when compared…
Weaning induces NOS-2 expression through NF-κB modulation in the lactating mammary gland: importance of GSH
Zaragozá, R; Miralles, VJ; Rus, AD; García, C; Carmena, R; García-Trevijano, ER; Barber, T; Pallardó, FV; Torres, L; Viña, JR. At the end of lactation the mammary gland undergoes involution, a process characterized by apoptosis of secretory cells and tissue remodelling. To gain insight into this process, we analysed the gene expression profile by oligonucleotide microarrays during lactation and after forced weaning. Up-regulation of inflammatory mediators and acute-phase response genes during weaning was found. Expression of IκBα (inhibitory κBα), a protein known to modulate NF-κB (nuclear factor-κB) nuclear translocation, was significantly up-regulated. On the other hand, there was a time-…
Improved nitrogen metabolism in rats fed on lipid-rich liquid diets
N metabolism was studied in young rats fed on lipid-rich, isonitrogenous, purified liquid diets, a convenient and easy technique for inducing voluntary overfeeding of energy and lipids under controlled nutritional conditions. Overfed rats showed a marked N retention at the expense of a reduced production of urea. The capacities of isolated hepatocytes to synthesize urea and glucose from added precursors were greatly diminished. The activities of the urea cycle enzymes and several enzymes involved in the availability of NH3, for this pathway were concomitantly reduced in overfed animals. Therefore, our results showed an improved N metabolism in overfed rats promoted by the overfeeding of lip…
Vitamin A deficiency alters the structure and collagen IV composition of rat renal basement membranes.
Retinoids can modulate the expression of extracellular matrix (ECM) proteins with variable results depending on other contributing factors. Because changes in these proteins may alter the composition and impair the function of specialized ECM structures such as basement membranes (BMs), we studied the effects of vitamin A deficiency on renal BMs during the growing period. Newborn male rats were fed a vitamin A-deficient (VAD) diet for 50 d. The ultrastructure of renal BMs was analyzed by electron microscopy. Total collagen IV, the different alpha(IV) chains, matrix degrading metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) were quantified by immunocytochemistry a…
Protein synthesisin vivoin rats fed on lipid-rich liquid diets
Changes in tissue composition and protein synthesis ratio were studied in the major tissues of the body in young rats fed on lipid-rich, isonitrogenous purified liquid diets, a convenient method for inducing voluntary overfeeding under controlled nutritional conditions. Overfed rats showed faster growth induced by the energy excess. Analysis of tissue composition (protein, DNA and RNA contents) revealed that growth was due mainly to tissue hyperplasia in which protein and DNA contents increased in parallel. Fractional protein synthesis ratio measuredin vivoby the flooding-dose method of phenylalanine showed a marked increase in all tissues. This change could be attributed to an increase in …
Regulation of the Urea Cycle during Lactation
We have recently shown that the uptake of amino acids by rat lactating mammary gland is 15 mmoles/day (1). This effect is achieved by an increase in food intake during lactation and probably by changes in amino acid metabolism in other tissues. Rat liver removes 75% of the total amino acids derived from a protein meal (2); therefore plays a key role in the regulation of plasma amino acid concentration.
Vitamin A Deficiency and Alterations in the Extracellular Matrix
Vitamin A or retinol which is the natural precursor of several biologically active metabolites can be considered the most multifunctional vitamin in mammals. Its deficiency is currently, along with protein malnutrition, the most serious and common nutritional disorder worldwide. It is necessary for normal embryonic development and postnatal tissue homeostasis, and exerts important effects on cell proliferation, differentiation and apoptosis. These actions are produced mainly by regulating the expression of a variety of proteins through transcriptional and non-transcriptional mechanisms. Extracellular matrix proteins are among those whose synthesis is known to be modulated by vitamin A. Reti…
Vitamin A Deficiency and the Lung.
Vitamin A (all-trans-retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are involved in a wide range of physiological processes such as embryonic development, vision, immunity and cellular differentiation and proliferation. Retinoic acid (RA) is the main active form of vitamin A and multiple genes respond to RA signalling through transcriptional and non-transcriptional mechanisms. Vitamin A deficiency (VAD) is a remarkable public health problem. An adequate vitamin A intake is required in early lung development, alveolar formation, tissue maintenance and regeneration. In fact, chronic VAD has b…
Vitamin A Deficiency Increases Protein Catabolism and Induces Urea Cycle Enzymes in Rats
Chronic vitamin A deficiency induces a substantial delay in the rates of weight and height gain in both humans and experimental animals. This effect has been associated with an impaired nutrient metabolism and loss of body protein. Therefore, we analyzed the effect of vitamin A deficiency on endogenous proteolysis and nitrogen metabolism and its reversibility with all-trans retinoic acid (RA). Male weanling rats, housed in pairs, were pair-fed a vitamin A-deficient (VAD) or control diet until they were 60 d old. A group of deficient rats were further treated with daily intraperitoneal injections of all-trans RA for 10 d. Final body and tissue (i.e. liver and heart) weights were significantl…
A Deficiency in Respiratory Complex I in Heart Mitochondria from Vitamin A-Deficient Rats Is Counteracted by an Increase in Coenzyme Q
Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been described in many congenital and acquired diseases. Administration of coenzyme Q (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases. However, the mechanisms by which CoQ exerts the therapeutic effects are not clearly understood. A reason could be the lack of saturation of CoQ, in kinetic terms, for complex I activity. However, this hypothesis has not been proved in vivo because of the difficulty to incorporate CoQ into the mitochondrial membranes. We have found a deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats which was accompanied by high CoQ…
Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland
GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.
Effect of a hyperlipidic diet on lipid composition, fluidity, and (Na+-K+)ATPase activity of rat erythrocyte membranes.
Feeding rats a hyperlipidic diet in which animals were offered daily a variety of high-energy food resulted in a significant increase of serum free fatty acids and a decrease of phospholipids with respect to controls. On the contrary, there were no significant differences in erythrocyte membrane total lipid composition between the two groups. Erythrocyte membranes showed a significant decrease in saturated fatty acid content and a significant increase in (n-6) polyunsaturated fatty acid content; (n-3) polyunsaturated fatty acids significantly decreased. Membrane fluidity, investigated by fluorescence polarization of diphenylhexatriene, significantly increased in the erythrocyte membranes of…
Vitamin A deficiency alters rat lung alveolar basement membrane: reversibility by retinoic acid.
Vitamin A is essential for lung development and pulmonary cell differentiation and its deficiency results in alterations of lung structure and function. Basement membranes (BMs) are also involved in those processes, and retinoic acid, the main biologically active form of vitamin A, influences the expression of extracellular matrix macromolecules. Therefore, we have analyzed the ultrastructure and collagen content of lung alveolar BM in growing rats deficient in vitamin A and the recovering effect of all-trans retinoic acid. Male weanling pups were fed a retinol-adequate or -deficient diet until they were 60 days old. A group of vitamin A-deficient pups were recovered by daily intraperitonea…
Elevated Expression of Liver γ-Cystathionase Is Required for the Maintenance of Lactation in Rats
Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionas…