Search PubMed⌕ Search

Biomedical subjects

L M Klevay

Publications and source records attributed to L M Klevay.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antioxidant enzyme gene transcription in copper-deficient rat liver.

Antioxidant enzymes, Cu/Zn- and Mn-superoxide dismutase, catalase, and glutathione peroxidase, constitute an important defense mechanism against cytotoxicity of reactive oxygen species. Copper is essential for the activity of Cu/Zn-superoxide dismutase. Oxidative stress, therefore, is expected in organs of rats fed copper-deficient diet due to reduced Cu/Zn-superoxide dismutase activity. Our previous studies have shown that the expression of antioxidant enzymes was altered in copper-deficient rat liver. The present report was undertaken to study further the transcription of these enzymes in liver nuclei of rats made copper-deficient for 4 weeks. While copper deficiency decreased the copper in liver by about 80%, it did not alter the copper content in liver nuclei. In spite of a 100% elevation in nuclear iron concentration, liver nuclei from copper-deficient rats showed normal appearance. The transcriptional rates for Cu/Zn-superoxide dismutase, glutathione peroxidase, and glyceraldehyde-3-phosphate dehydrogenase were not altered by dietary copper deprivation. In contrast, transcriptional rates for Mn-superoxide dismutase and beta-actin were increased but that for catalase was reduced in the nuclei isolated from the copper-deficient rat liver. These results suggest that oxidative stress, resulting from copper deficiency, differentially modulates the gene transcription for the antioxidant enzymes in rat liver.

Animals↗
PubMed1996

Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations about copper.

Important aspects of copper nutrition were collected from all 10 editions of the Recommended Dietary Allowance along with the history of the paradigm concept according to Thomas Kuhn. Important anomalies in copper nutrition, such as the easy accessibility to diets containing considerably less copper than the estimated safe and adequate daily dietary intake are reviewed. Important experiments with animals are compared with copper depletion experiments with humans. Data support the belief that people respond to diets low in copper similarly to animals and that measurement of copper in blood plasma generally is useless in assessing nutritional status. If common diets low in copper are consumed regularly during pregnancy, maternal stores of copper will be depleted. Although there is some evidence of lower copper in heart and major blood vessels in elderly people, it is premature to suggest different intakes for adults of different ages. Although consideration of cardiovascular data in establishing an RDA for copper may seem to be a new paradigm, considerations of general health and well being have long contributed to establishing RDAs. Dietary copper can be increased by adhering to the advice symbolized by the food pyramid.

Adult↗
PubMed1995

Role of intracellular SOD in oxidant-induced injury to normal and copper-deficient cardiac myocytes.

Previous studies have shown that susceptibilities of hepatocytes and endothelial cells to H2O(2)-induced injury are altered by changes in the intracellular activity of Cu,Zn-containing superoxide dismutase (CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in oxidant-induced injury to rat cardiac myocytes, cells with reduced CuZn-SOD activity but normal ATP content were either isolated from the hearts of adult copper-deficient rats or obtained by treatment of normal isolated adult myocytes with diethyldithiocarbamate. These myocytes and controls with normal CuZn-SOD activity were exposed to either reagent H2O2 or oxidants generated by extracellular glucose oxidase plus glucose or xanthine oxidase plus xanthine. It was shown that myocytes with CuZn-SOD activities reduced by 70-90% were equally susceptible to H2O2 and the two oxidant-generating systems as the control myocytes. The findings suggest that in adult cardiac myocytes, in contrast to the situation in some other cells, intracellular CuZn-SOD may not have a significant defensive role against acute H2O(2)-induced injury. The possibility remains, however, that changes in the activity of this enzyme, e.g., in copper deficiency, may be relevant to the ability of myocytes to cope with chronic oxidative stress resulting from imbalance between intracellular oxygen radical-generating and -scavenging systems.

Adenosine Triphosphate↗
PubMed1995

Blood pressure and heat shock protein expression in response to acute and chronic stress.

We previously demonstrated that restraint and pharmacological agents that activate sympathetic nervous system activity induce expression of the 70-kD heat shock protein (HSP70) in major blood vessels. The magnitude and rapidity in which HSP70 is induced in the aorta suggest that it may play a salient role in the mechanical properties of vascular smooth muscle. Other investigators have reported that HSP70 inducibility is increased in genetically hypertensive animals. In this report, we have investigated the effects of acute and chronic (8-week) exposure to restraint and restraint in the presence of a randomized intermittent air jet on the development of hypertension and the induction of HSP70 in the aorta and adrenal glands of normotensive adult male Sprague-Dawley rats. Acute restraint or air jet resulted in a fivefold to sixfold increase in aortic HSP70 mRNA expression. Chronic exposure to restraint reduced the HSP70 response to acute restraint. In contrast, no adaptation of the HSP70 response to acute air jet was observed in aortas of chronically air jet-treated rats. In adrenal glands, HSP70 expression was reduced after chronic restraint and air jet, indicating that in this tissue, adaptation occurs to both stressors. There was no difference in HSP70 expression in unstressed rats that had been chronically exposed to restraint or air jet in either adrenal gland or aorta. A significant increase (P < .05) in systolic blood pressure developed in air jet-treated animals (120 +/- 3 mm Hg) but not in restrained rats (107 +/- 2 mm Hg) compared with unstressed controls (106 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient rats.

OBJECTIVE: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart. METHODS: Copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were compared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms. RESULTS: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of alpha 1 and alpha 2 isoforms, and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. CONCLUSIONS: In the rat ventricular tissue, oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.

Animals↗
PubMed1994

Differential regulation of superoxide dismutase in copper-deficient rat organs.

The effects of dietary copper deprivation on the activities, immunoreactive protein concentrations, and mRNA abundance of copper/zinc- and manganese-superoxide dismutase (Cu/Zn- and Mn-SOD) were examined in liver, heart, and brain of weanling rats fed a Cu-deficient diet for 4 weeks. Hepatic Cu/Zn-SOD activity, enzyme content, and mRNA abundance were significantly reduced, and, conversely, the activity, protein, and mRNA levels of Mn-SOD were significantly elevated in Cu-deficient rats. In Cu-deficient heart, the activity and protein content for Cu/Zn-SOD were reduced, whereas those for Mn-SOD were increased; the levels of mRNAs for these two enzymes was unaffected. Dietary Cu deficiency was without effect on the activities, enzyme contents, and mRNA abundance of brain Cu/Zn- and Mn-SOD. These results indicate that SODs from liver, heart, and brain exhibit differential sensitivities to dietary Cu deprivation, and that different mechanisms (transcriptional, posttranscriptional, or posttranslational) may be involved in their regulation.

Animals↗
PubMed1994

Copper: an antioxidant nutrient for cardiovascular health.

Dietary copper often is low in the Western diet; low intakes may affect all stages of atherosclerosis adversely. Impaired oxidative defense in copper deficiency contributes to hypercholesterolemia, hypertension, and impaired prostaglandin metabolism. Free copper ion does not exist in vivo; some in-vitro experiments are conducted with millions-fold excesses.

Antioxidants↗
PubMed1994

Contrasting effects of a dietary copper deficiency in male and female mice.

Female rats are protected from the lethal effects of a dietary copper (Cu) deficiency, but female mice fed a Cu-deficient diet develop atrial thromboses and die. To further investigate the effect of sex on Cu status in mice (n = 16), male and female adult Swiss-Webster mice were fed Cu-supplemented (8.4 mg Cu/kg) or Cu-deficient (0.3 mg Cu/kg) diets with deionized water for 43-49 days. Six female mice, but only one male mouse, fed the Cu-deficient diet died during the experiment. Both male and female mice fed the Cu-deficient diet exhibited typical features of deficiency. The severity of anemia and the values observed for several indicators of Cu status (plasma ceruloplasmin [EC 1.16.3.1.] and erythrocyte copper-zinc superoxide dismutase [EC 1.15.1.1.] activities, cardiac Cu) were similar in both male and female Cu-deficient mice. However, cardiac enlargement (0.97 vs 0.73 g/100 g body wt, P < 0.05), cardiac edema (79.9% vs 78.2% cardiac water, P < 0.05) and depletion of renal Cu (10.4 vs 12.5 micrograms/g dry weight, P < 0.05) were more severe in female compared with male, Cu-deficient mice. Furthermore, although hepatic Cu was significantly (P < 0.05) lower in female Cu-deficient compared with Cu-supplemented mice, it was not significantly decreased by deficiency in male mice. These data indicate that the female mice experienced a more extreme form of Cu deficiency than the males.

Analysis of Variance↗
PubMed1993

Comparative responses of rats to different copper intakes and modes of supplementation.

Purified diets deficient in copper and based on either sucrose, egg white, and corn oil or sucrose, casein, corn starch, and safflower oil were fed to young rats. Graded amounts of copper were supplied in drinking solutions with the former diet and by addition to the latter diet; anatomical, chemical, and physiologic responses were compared. Three micrograms Cu/ml and 5 micrograms Cu/g were sufficient to maximize the direct assessments of copper nutriture (copper in blood plasma, heart, and liver). Nutritional adequacy by indirect criteria (heart iron, plasma ceruloplasmin, heart weight divided by body weight, plasma cholesterol, and body weight) generally was found with 3 micrograms/ml and 4 micrograms/g. Anemia was an insensitive characteristic of deficiency. Liver iron was minimized by 4 micrograms Cu/ml and 5 micrograms Cu/g. Most of the differences in response to copper added to water in comparison to copper added to diet probably were explained by the lower amount of copper in the casein diet. Responses to the two dietary regimens were similar when variables were plotted against liver copper. Correlation coefficients with liver copper ranged from 0.52 for liver zinc to 0.96 for heart iron. Liver copper probably is the best index of copper nutriture.

Animals↗
PubMed1993

Ischemic heart disease: nutrition or pharmacotherapy?

There are many diseases of unknown etiology. Increasingly vibrant, contemporary research is attempting to associate trace element metabolism with some of these illnesses. Because trace elements can produce profound effects on health via enzymes, hormones and messenger molecules, analytical assessment must be directed toward these chemicals as well as to the trace elements. Element analysis may be directed best toward specific cells, tissues and organs. Copper deficiency is associated with the etiology, pathogenesis and pathophysiology of ischemic heart disease via metabolic processes affecting cardiovascular health. Some drugs now used to treat heart disease affect copper metabolism but many other metabolic processes are unaffected by deficiency. It seems prudent to avoid diets containing amounts of copper that have been proved insufficient for people in controlled experiments.

Animals↗