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Biomedical subjects

R B Rucker

Publications and source records attributed to R B Rucker.

At least 55 records · Page 3Linked to original sources
PubMed1987

The effects of ozone on lung, heart, and liver superoxide dismutase and glutathione peroxidase activities in the protein-deficient rat.

The effects of protein deficiency or food restriction and ozone exposure on lung, heart and liver superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were studied in weanling and adult rats. Two groups of rats were fed diets containing 4 or 16% protein. A third group was fed the 16% protein diet, but at the level consumed by the rats fed the 4% protein diet. After 3 weeks (weanling) or 5 weeks (adult), one-half of the rats in each group were exposed continuously to 0.64 ppm ozone for 7 days. In adult rat lung, O3 exposure typically stimulated Cu,Zn-SOD and GPx activities in all groups, but in weanling rats only GPx activity was elevated and only in rats fed the 16% protein diet. Liver Cu,Zn-SOD activity was also influenced by diet; in adult rats, liver Mn-SOD and GPx activities were often depressed following O3 exposure. Heart SOD and GPx, however, were not affected by ozone or diet. The pulmonary and hepatic effects due to diet and O3 further illustrate the importance of nutritional status when assessing the health effects of O3 exposure.

Animals↗
PubMed1986

Tropoelastin production and tropoelastin messenger RNA activity. Relationship to copper and elastin cross-linking in chick aorta.

The elastin content of the chick thoracic aorta increases 2--3-fold during the first 3 weeks post-hatching. The deposition of elastin requires the covalent cross-linking of tropoelastin by means of lysine-derived cross-links. This process is sensitive to dietary copper intake, since copper serves as cofactor for lysyl oxidase, the enzyme that catalyses the oxidative deamination of the lysine residues involved in cross-link formation. Disruption of cross-linking alters tissue concentrations of both elastin and tropoelastin and results in a net decrease in aortic elastin content. Autoregulation of tropoelastin synthesis by changes in the pool sizes of elastin or tropoelastin has been suggested as a possible mechanism for the diminished aortic elastin content. Consequently, dietary copper deficiency was induced to study the effect of impaired elastin cross-link formation on tropoelastin synthesis. Elastin in aortae from copper-deficient chicks was only two-thirds to one-half the amount measured in copper-supplemented chicks, whereas copper-deficient concentrations of tropoelastin in aorta were at least 5-fold higher than normal. In spite of these changes, however, increased amounts of tropoelastin, copper deficiency and decreased amounts of elastin did not influence the amounts of functional elastin mRNA in aorta. Likewise, the production of tropoelastin in aorta explants was the same whether the explants were taken from copper-sufficient or -deficient birds. The lower accumulation of elastin in aorta from copper-deficient chicks appeared to be due to extracellular proteolysis, rather than to a decrease in the rate of synthesis. Electrophoresis of aorta extracts, followed by immunological detection of tropoelastin-derived products, indicated degradation products in aortae from copper-deficient birds. In extracts of aortae from copper-sufficient chicks, tropoelastin was not degraded and appeared to be incorporated into elastin without further proteolytic processing.

Animals↗
PubMed1986

Role of plasma and serum proteases in the degradation of elastin.

Accelerated proteolysis of tropoelastin and elastin occurs in the major arteries of chicks fed copper-deficient diets. Signs of elastin degradation are not obvious in normal arteries of copper-supplemented chicks. It is proposed that the sources of proteases that effect elastin degradation are from plasma and serum. Both calcium-dependent proteases and kallikrein were effective in degrading tropoelastin and partially crosslinked insoluble elastin into peptides similar to those detected in aortic extracts from copper-deficient chicks. As dietary copper deficiency progresses it is also possible to detect elastin peptides in plasma.

Animals↗
PubMed1986

Lung collagen and elastin after ozone exposure in vitamin B-6-deficient rats.

The effects of vitamin B-6 deficiency and ozone exposure on selected features of connective tissue metabolism in lung were investigated in groups of weanling male rats fed one of three diets: B-6-supplemented, fed ad lib; B-6-deficient, fed ad lib; or B-6-supplemented, restricted to the food intake of deficient rats for 5 weeks. Also, perinatal rat pups were studied that were nursed from dams fed one of the 3 diets from parturition to day 15 of lactation. During the final week of each experiment, half of the rats in each of the groups were exposed to 0.64 ppm of ozone (23.5 h per day). The collagen and elastin content, collagen synthesis rate, total protein synthesis rate, and lysyloxidase activity of lungs were measured. Perinatal pups rendered vitamin B-6-deficient were particularly sensitive to ozone exposure (65% died as compared to fewer than 5% of the ad lib or food-restricted controls). When L-proline incorporation into collagen and total protein was investigated using lung minces, food restriction and B-6-deficiency resulted in about one-half the incorporation normally observed. Total lung lysyl oxidase activity was also decreased in B-6-deficient and food-restricted rats compared to B-6-supplemented rats fed ad lib. Exposure to ozone resulted in increased lysyl oxidase activity and collagen synthesis in lungs from B-6-supplemented rats, but such responses were not observed in B-6-deficient or food-restricted (FR) rats exposed to ozone.

Aging↗
PubMed1985

Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups.

Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.

Amino Acids↗
PubMed1985

Changes in response to ascorbic acid administered orally to rat pups: lung collagen, elastin and protein synthesis.

Rat pups were supplemented orally with high doses of L-ascorbic acid (AA) or D-isoascorbic acid (IA) throughout suckling. The regulation of AA in the lung and its relationship to collagen and elastin deposition were examined. Based on known responses of smooth muscle cells and fibroblasts in culture to high concentrations of AA, it was hypothesized that a markedly elevated intake of AA should increase net collagen deposition, but decrease net elastin deposition in the neonatal rat lung. In two experiments, groups of rat pups were gavaged daily with AA (in saline), in amounts corresponding to 0.1, 1 or 2% of the total consumed milk solids. As controls, pups were gavaged with IA (2% of the milk solids) or saline. The treatments were initiated 2 d postpartum and continued for 19 or 23 d. Compared to the saline-gavaged pups. AA and IA were elevated (twofold) in serum and lung at d 11, but not at d 25. Urinary excretion represented a major route for elimination of excess AA and IA. With respect to collagen and elastin accumulation, only elastin consistently was altered (10-20% decrease) in groups supplemented with AA or IA at the termination of experiments. The rodent appears to defend against elevation of AA concentration in the lung. Consequently, the putative effects of AA on the net deposition of lung collagen and elastin in vivo are less obvious than effects reported by others from in vitro studies.

Administration, Oral↗
PubMed1985

Effects of protein deficiency and food restriction on lung ascorbic acid and glutathione in rats exposed to ozone.

Weanling (52 +/- 4 g) or adult (259 +/- 16 g) male Sprague-Dawley rats were fed ad libitum casein-based diets containing 4 or 16% protein. A third group (food restricted) was fed daily the 16% protein diet, but at the food intake level of the 4% protein group. After 3 wk (weanling) or 5 wk (adults), half of the rats in each group were continuously exposed to 0.64 ppm ozone for 7 d. Ascorbic acid and reduced glutathione levels were then measured. In the heart and liver from weanling rats, ascorbic acid concentrations were lower in the protein-deficient group than in either control group. In the liver from weanling rats glutathione concentrations were also reduced in response to protein deficiency. Exposure to ozone produced no additional response. For adult rats the response for liver glutathione was similar to that of the weanlings. The liver ascorbate concentration, however, was consistently lower in adult rats compared to weanlings exposed to ozone. In lungs from adult rats, the ascorbic acid concentration was lower in the protein-deficient group than in either control group. On a whole-organ basis, both ascorbic acid and glutathione were usually higher in lungs from rats exposed to ozone than from those exposed to air. Interestingly, protein deficiency did not appear to compromise the lung's ability to maintain, in relative terms, the ascorbic acid or glutathione concentration in response to ozone.

Aging↗
PubMed1985

Elastin metabolism during perinatal lung development in the copper-deficient rat.

Metal-chelating drugs were employed to investigate the role of copper (Cu) in elastin metabolism during the period of alveolarization in rat lung. Six groups of pregnant Sprague-Dawley rats were fed one of six semipurified diets, i.e., sufficient or deficient in copper, or the same basal diet containing 0.2% or 0.4% D-penicillamine (DPA), or the same basal diet containing 0.2% or 0.4% triethylenetetramine (TETA). The dams were fed throughout gestation, parturition, and lactation. The pups were then killed postnatally at day 10 and day 21 for the various analyses. At day 21, liver copper in the Cu-deficient pups was 3-5% control levels. In drug-treated groups, liver copper was 16-30% control levels. In the 21-day-old Cu-deficient rats, the concentration of lung elastin was only 75% of its concentration in control. Lung lysyl oxidase activity was lower in Cu-deficient rats, and data for the relative distribution of lung elastin cross-linking amino acids indicated impaired cross-linking in the pups from both the Cu-deficient and the 0.4% DPA groups. Morphologic examination of the lung also indicated dilation of airways in these two groups. Data on the distribution of cross-linking amino acids in elastin samples were also consistent with previous suggestions that impaired cross-linking observed in copper deficiency or from DPA treatment results from different mechanisms. Since the intakes of DPA and TETA were chosen to be in the therapeutic range of intakes used to treat diseases of abnormal copper metabolism, an important feature of these studies is that DPA and perhaps TETA have the potential of impairing normal lung development.

Animals↗
PubMed1984

Long-term consequences of exposure to ozone. I. Lung collagen content.

Lung collagen content of rats and monkeys (Macaca fascicularis) exposed to ozone for 1 to 13 weeks and for 1 year, respectively, was quantified by measurement of 4-hydroxyproline in hydrolysates of whole lungs. In addition, ratios of type I to type III collagen in the lungs of the same monkeys were also evaluated by cyanogen bromide peptide mapping techniques. We observed elevated levels of collagen in lungs of both species of animals exposed to ozone. We conclude that elevations in collagen synthesis rates in lungs of rats and monkeys acutely exposed to high levels of ozone are reflected by corresponding increases in lung collagen content over subchronic and chronic time frames. Preliminary results on young rats also suggest that removal of rats from atmospheres containing ozone does not cause reversal of such increases in lung collagen content. To the contrary, recovery periods of up to 6 weeks seem to exacerbate the observed increases in lung collagen content.

Animals↗
PubMed1984

Ozone exposure, food restriction and protein deficiency: changes in collagen and elastin in rodent lung.

Two groups of weanling or young adult rats were fed ad lib casein-based diets containing 4 or 16% protein. Food was restricted in a third group (fed the 16% protein diet) to the amount consumed daily by rats (adult or weanlings) fed the 4% diet. After 3 weeks (weanlings) or 1, 3 or 5 weeks (adults), one-half of the rats in each group were exposed to 0.64 ppm (1.28 mg/m3) of ozone for 7 days (23.5 h each day). Several parameters were then evaluated related to lung connective tissue metabolism including: (1) total lung hydroxyproline, (2) total lung elastin, (3) apparent rates for lung collagen synthesis and elastin accumulation and (4) lung and body weights. In general, the response to protein deficiency and food restriction was more pronounced than to ozone exposure. Protein deficiency and food restriction resulted in decreased lung size and collagen content. However, the ability of lung to respond to ozone (in relative terms) was not altered by changes in diet as assessed by changes in lung weight or the collagen synthetic rate.

Animals↗
PubMed1984

Elastin metabolism and chemistry: potential roles in lung development and structure.

Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization . A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine , merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed.

Amino Acids↗
PubMed1983

Elastin synthesis during perinatal lung development in the rat.

The rate of soluble elastin synthesis was estimated in lung explants from rats of differing ages to better define periods in lung development important to the deposition of lung elastin. Lungs from rat pups at days 1, 3, 7, 9, 12, 15, and 21 post-parturition and from adult rats were incubated in a defined medium containing L-[3H]valine. Following incubation, labelled soluble elastin (tropoelastin) was separated from other soluble proteins by coacervation and electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate. The tropoelastin synthetic rate was then estimated after correcting for differences in recovery of radioactivity as tropoelastin and lung tissue L-[3H]valine specific activity. Maximal rates of elastin synthesis were observed in lung explants from 7-12-day-old rats. The rate of elastin synthesis during this period was 5-8-times the rate observed in adult rat lung (expressed per g of fresh lung) and represented approx. 2% of the total protein synthesis. Moreover, the values derived from lung explant culture for elastin synthesis were consistent with values for lung elastin deposition in the perinatal rat (5-10 micrograms elastin/h per g lung).

Aging↗
PubMed1983

Modification of arterial elastin in vivo. Effects of age and diet on changes in the N-terminal amino acid content of aorta elastin.

We have previously demonstrated that aorta elastin, a highly crosslinked protein, does not undergo turnover that is easily measured in vivo. Therefore, it was hypothesized that when proteolysis of elastin occurs, a positive increase in N-terminal amino acids should result. Such an increase would represent elastin-derived fragments held covalently in situ. A cyanate carbamylation procedure was used to estimate the changes in N-terminal amino acids in aorta elastin. To provide tissue for the studies, Japanese quail (3 weeks old) were fed diets with or without the addition of 1% cholesterol. It was found that, in normal birds, the number of N-terminal amino acid residues increased from two to approximately three residues per 800 total residues (or mole of tropoelastin) throughout sexual development (3 to 8 weeks, post-hatching), with little increase thereafter. In hypercholesterolemic birds, the rate of appearance of new N-terminal residues, particularly glutamine or glutamic acid, appeared enhanced throughout early development, but by sexual maturity the number of N-terminal amino acid residues in aorta elastin from cholesterol-fed birds was similar to that for the control birds. For each of the elastin samples analyzed, approximately one residue of glycine was recovered per 800 total residues. Other amino acids that predominated as N-terminal residues were serine, aspartic and glutamic acids.

Aging↗
PubMed1983

Morphological and biochemical features of elastase-induced emphysema in strain A/J mice.

Elastase-induced animal models of pulmonary emphysema are potentially useful to study the physiological, anatomical, and biochemical injuries associated with emphysema. After the endotracheal instillation of porcine pancreatic elastase (0.15 or 0.30 mg elastase per 100 g body weight) into strain A/J mice, selected biochemical and morphometric indices od lung damage were examined. Elastase produced extensive air space enlargement without appreciable mortality. Lesions involving the lung parenchyma distal to the terminal bronchioles were observed within 2 weeks and possessed features resembling panlobular and centrilobular emphysema. Morphometric analyses of emphysema indicated that after the acute phase of tissue damage and repair, the lesions stabilize without further deterioration of alveolar structure. Increased lung elastin synthesis was noted following endotracheal elastase, resulting in lung elastin levels 30% higher than controls 8 weeks after treatment. Minimal alterations to lung DNA and protein levels indicated that elastase produced specific lung lesions exclusive of inflammation and edema.

Animals↗
PubMed1983

Selected features of copper metabolism in the cat.

In separate experiments, domestic short hair kittens were fed diets based on soy or egg white protein containing from 1.98 to 9.64 or 0.58 to 9.8 micrograms Cu/g diet, respectively. Moreover, kittens were also nursed from queens fed diets containing either 0.58 or 12 micrograms Cu/g of diet. In each experiment, copper was analyzed in liver, spleen, lung, heart, muscle and brain samples. The liver copper concentration was the most responsive to changes in dietary copper intake. For example, in weanling kittens fed 0.58 or 9.8 micrograms Cu/g diet, the liver copper concentration was 24 or 45 micrograms/g wet weight, respectively. Likewise, the levels of hepatic Cu,Zn-superoxide dismutase were reduced in kittens fed the low copper diet. However, the concentrations of zinc, iron and manganese in liver, lung, spleen, brain, muscle and kidney were not consistently changed in response to low copper intakes. Anemia was also not a consistent feature in the copper-deficient cat or kitten, but signs of connective tissue lesions were observed in kittens born to and weaned from queens fed diets containing less than 1 micrograms Cu/g diet. Based on these observations and data for changes in growth in response to the differing levels of dietary copper, the copper requirement for the kitten was estimated to be 4-5 micrograms/g of diet (energy content approximately 5 kcal or 21 kJ per gram).

Age Factors↗
PubMed1983

Protein deficiency: effects on lung mechanics and the accumulation of collagen and elastin in rat lung.

Groups of weanling (approximately 50 g) or young adult (approximately 300 g) rats were fed ad libitum casein-based diets varying in protein content from 4 to 16%. A group was also fed the 16% protein diet in an amount on a daily basis restricted to that consumed by the protein-deficient group (4% protein). The rats were fed the diets for either 4 weeks (weanling) or 6 weeks (adults). Protein-deficient or "food-restricted" rats (whether weanling or adults) were smaller and had smaller lungs than rats fed ad libitum the diets containing 16% protein. The lung elastin content was more resistant to dietary manipulation than was the lung collagen content. Lung collagen was significantly decreased in both weanling and adult rats fed the 4% protein diet. In weanling rats, pressure-volume relationships derived from saline-filled lungs (analyzed by exponential curve-fitting methods) suggested that lungs from food-restricted rats may be less compliant than lungs from rats fed the control diet ad libitum. When expressed in absolute terms, lungs from protein-deficient rats also appeared to be less compliant than normal rats; however, on a relative basis (percentage of volume at a given recoil pressure or the expression of volume on a weight basis) differences in compliance were less apparent. It is proposed that in weanling rats the differences in lung composition and compliance are the result of retarded lung growth and perhaps development.

Age Factors↗