metallothionein and Starvation

Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but instead has a much more pleiotropic character. There is now ample evidence that leptin has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review we have focused on the effects of leptin in the antigen-specific immunity and in the inflammatory effector system.

Topics: Adaptation, Physiological; alpha-MSH; Animals; Anorexia; Humans; Immunity; Inflammation; Leptin; Macrophages; Metallothionein; Monocytes; Receptors, Cell Surface; Receptors, Leptin; Starvation; Systemic Inflammatory Response Syndrome; T-Lymphocytes

Leptin was originally identified as an adipocyte-derived cytokine with a key role in the regulation of the energy balance. Subsequent research has, however, revealed that leptin's biological action is not restricted to its effects on appetite and food intake, but rather has a much more pleiotropic character. Evidence is now accumulating that it has important functions in reproduction, hematopoiesis, HPA-axis endocrinology and angiogenesis. In this review, we have focused on the effects of leptin in the immune system, which can be found in both the antigen-specific immunity and in the inflammatory effector system.

Topics: Adaptation, Physiological; Animals; Humans; Immunity; Immunity, Cellular; Inflammation; Leptin; Metallothionein; Neuropeptide Y; Starvation; Systemic Inflammatory Response Syndrome; T-Lymphocytes

Values of five biomarkers related to cell stress or pollution were evaluated in tissues of the land snail Eobania vermiculata under starvation or hibernation conditions. The biomarkers applied were lysosomal membrane stability in digestive gland cells (LMS) or in haemocytes (neutral red retention assay (NRR)), acetylcholinesterase activity (AchE; EC 3.1.1.7), metallothionein content (MTs), and cyclic AMP content (cAMP). Three groups of snails were studied that were kept under starvation, hibernation and normal conditions, respectively. The results indicated statistically lower values of LMS and NRR in snails kept under starvation or hibernation compared to control ones. Higher values of AChE activity were measured in snails under hibernation compared to controls. MT contents were statistically higher in snails under starvation compared to controls. Measurement of cAMP contents showed no significant differences among the tested groups. The values of the first four biomarkers may be affected by factors other than pollution, such as starvation or hibernation. Therefore, these factors should be taken into consideration when biomonitoring studies are performed in time intervals of hibernation or starvation.

Topics: Acetylcholinesterase; Analysis of Variance; Animals; Biomarkers; Environmental Monitoring; Greece; Hibernation; Lysosomes; Metallothionein; Neutral Red; Snails; Starvation

The aim of this study was to assess the intensity of enzymatic antioxidative parameters [i.e., superoxide dismutase (SOD), catalase (CAT), and the glutathione peroxidases each selene dependent, GPOX or selene independent, including GSTPx, glutathione S-transferase, and GST] and non-enzymatic antioxidative parameters [i.e., glutathione total (GSH-t), the heat shock proteins of Hsp70, and metallothioneins (Mt)] in the midgut glands of female and male wolf spiders Xerolycosa nemoralis (Lycosidae) exposed to natural stressors (i.e., heat shock and starvation) and anthropogenic stressors (i.e., the organophosphorous pesticide dimethoate) under laboratory conditions. The spiders were collected from two differentially polluted sites both localized in southern Poland: Olkusz, which is heavily polluted with metals, and Pilica, the reference site. In response to the stressing factors, increases in Hsp70 levels, in the concentrations of total glutathione and in the activity levels of glutathione-dependent enzymes (GPOX, GSTPx, and GST) were found in the midgut glands of males. In the females, high levels of activity of CAT and SOD were revealed, as well as an increased percentage of Mt-positive cells. Preexposed females, in comparison to the individuals from the reference site, responded with increased SOD activity, irrespective of the stressing factor. In contrast, the changes in the antioxidative parameters in the midgut glands of male X. nemoralis seem to reflect a short-term reaction to the applied stressors and do not confirm the effects of long-term selection in a polluted environment.

Topics: Analysis of Variance; Animals; Antioxidants; Catalase; Digestive System; Dimethoate; Female; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Hot Temperature; HSP70 Heat-Shock Proteins; Insecticides; Male; Metallothionein; Sex Factors; Spiders; Starvation; Stress, Physiological; Superoxide Dismutase

An indoor exposure experiment with juvenile Babylonia areolata was conducted to study its survival, growth, cadmium (Cd) accumulation, metallothionein (MT) induction, and glycogen content as well as the DNA integrity of hepatopancreas tissue. The juveniles were starved or fed with mussel (Perna viridis) or clamworm (Perinereis aibuhitensis), and exposed to 50 microg x L(-1) of Cd2+ for 10 weeks. Prolonged starvation and simultaneous exposure to Cd reduced the survival rate of B. areolata, and its glycogen was mobilized in great extent. Feeding with P. viridis or P. aibuhitensis helped the B. areolata to combat Cd toxicity and lessen mortality. After exposed to Cd, the damage of the DNA integrity of hepatopancreas tissue for the B. areolata fed with P. viridis or P. aibuhitensis could be recovered with time, but not for the starved B. areolata. Prolonged starvation caused tissue atrophy and led to Cd accumulation and MT increase, while feeding with P. viridis or P. aibuhitensis increased the B. areolata mass and lowered the Cd accumulation and MT level because of the tissue dilution effect. The B. areolata fed with P. viridis had better growth and lower Cd content than that fed with P. aibuhitensis. This study indicated that starvation intensified the toxicity of Cd to B. areolata, while prey type had significant effects on the growth rate of the B. areolata and indirectly affected its Cd accumulation, MT induction, and glycogen consumption. It was suggested that when using gastropods such as B. areolata as the indicator species to monitor marine environmental pollution, it would be necessary to consider the effects of habitat ecological data including food richness and prey type. Moreover, in the high-density cultivation of B. areolata in factory, rational feeding and periodic measurement of Cd concentration in seawater should be made.

Topics: Animals; Cadmium; DNA Damage; Glycogen; Metallothionein; Snails; Starvation; Water Pollutants, Chemical

Starved and fed carp (Cyprinus carpio) were exposed to sublethal waterborne copper exposure (1 microM) for 28 d in softened Antwerp, Belgium, city tap water. Copper accumulation in liver and gill tissues was determined, and changes in branchial Na+/K+-adenosine 5'-triphosphatase (ATPase) activity and metallothionein (MT) induction in gill and liver tissues were investigated following 28-d copper exposure. Gill Na+/K+-ATPase activity in exposed fish, both starved and fed, was at its lowest values after 3 d of exposure, after which it slowly recovered to preexposure values. No significant differences in branchial Na+/K+-ATPase activity were found between starved and fed fish. Copper accumulation in the liver and gills of the exposed starved carp was significantly higher than that in the exposed fed carp. The highest MT induction was found in liver tissues. Different patterns of MT induction were observed in the starved and fed carp during copper exposure. Before exposure, MT concentrations in the livers of the starved fish were significantly higher than those in the fed ones. Copper exposure significantly increased MT concentration in the liver of the fed fish, but no changes occurred in the starved fish. In contrast, copper exposure increased MT concentrations in the gills of the starved fish during the first week of exposure, whereas only a slight increase in MT concentration in the gills of the fed fish was observed. When taking into account the role of feeding status in MT induction, hepatic MT was a more relevant indicator for long-term monitoring of copper pollution in carp, but gill MT provided useful information regarding short-term copper toxicity.

Topics: Animals; Carps; Copper; Gills; Liver; Metallothionein; Sodium-Potassium-Exchanging ATPase; Starvation; Water Pollutants, Chemical

Metallothionein (MT) is induced in the liver not only by heavy metals, but also by stress such as starvation. However, the meaning of the induced MT during starvation has never been clear. In this study, we investigated the relationship between changes in hepatic MT synthesis and the hepatic damage that occurs during starvation. MT synthesis was assessed by measuring MT contents and the expression of the MT gene in the liver. The hepatic damage was assessed by measuring glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in the serum. MT synthesis in the liver increased over the normal level by starvation, but decreased under the normal level by refeeding after starvation. Both GPT and GOT activities of the refeeding group were higher than those of the control group. However, MT synthesis increased by a subcutaneous injection with CdCl(2) (1 mg Cd /kg) at the same time as refeeding after starvation. At this point, GOT activity decreased until it reached the normal level. MT synthesis decreased by refeeding after starvation, and from the results found in this study, we proposed the hypothesis that the liver damage caused by refeeding after starvation might be due to the decrease in the synthesis of a sufficient amount of MT induced by metals.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cadmium Chloride; Food; Gene Expression Regulation; Injections, Subcutaneous; Liver; Liver Diseases; Male; Metallothionein; Mice; Mice, Inbred Strains; RNA, Messenger; Spain; Starvation; Time Factors

Dogwhelks Nucella lapillus feed mainly on mussels and barnacles, and may experience periods of starvation. We report effects of nutritional state and prey type on the survival, growth, cadmium (Cd) accumulation, metallothionein (MT) induction and glycogen stores in N. lapillus exposed to Cd in water. Adult dogwhelks, with similar shell length (30.0+/-1.5 mm), were either starved or fed to satiation with barnacles Semibalanus balanoides, mussels Mytilus edulis or Cd-dosed M. edulis, and kept in filtered natural seawater (< 0.01 microg Cd 1(-1)) or Cd-contaminated (400 microg Cd 1(-1)) seawater for 80 days. Mortality and individual growth rate were determined. Cd, MT and glycogen were measured in different tissues. Prolonged starvation and exposure to Cd significantly reduced the survivorship of N. lapillus, but feeding could help dogwhelks to combat Cd toxicity and minimise mortality. Extended starvation also caused tissue wastage, leading to higher concentrations of Cd and MT in tissues, whereas fed animals increased in weight and had lower Cd and MT concentrations because of the tissue dilution effect. Prey type significantly affected growth rate of dogwhelks and indirectly influenced Cd accumulation, MT induction and glycogen stores. Eating mussels promoted better growth and higher glycogen reserves than eating barnacles. Individual growth rate decreased with increasing Cd accumulation. Cd-exposed survivors grew faster and consumed more than control animals, implying that these survivors may have better fitness and greater tolerance to Cd toxicity. The use of growth, condition index, MT and glycogen as biomarkers of environmental pollution are discussed. These results indicate a need to incorporate biological data including growth (or at least condition index) and prey type into biomonitoring programmes to allow sound interpretation.

Topics: Animals; Body Weight; Cadmium; Environmental Exposure; Food Chain; Glycogen; Metallothionein; Mollusca; Nutritional Status; Predatory Behavior; Starvation; Tissue Distribution; Water Pollutants, Chemical

Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine the influence of MT on Zn retention and the metabolic consequences of 2 d food deprivation, with and without inflammation induced by intraperitoneal injection of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn concentration in MT+/+ mice from 5.9 +/- 0.2 micromol/g on d 1 to 2.2 +/- 0.2 micromol/g on d 2, but not in MT-/- mice, 5.9 +/- 0.2 and 5.7 +/- 0. 5 micromol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d did not lower fecal Zn concentration in either genotype, although in MT+/+ mice, urinary Zn excretion was reduced from 12.7 +/- 1.3 nmol on d 1 to 5.9 +/- 1.8 nmol on d 2 and plasma Zn concentration was lowered to 9.8 +/- 0.4 micromol/L. Zn was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8 +/- 2.0 nmol on d 1, 9.3 +/- 2.9 nmol on d 2 and 13.0 +/- 1.0 micromol/L. LPS injection resulted in much higher total liver Zn (677 +/- 27 nmol) and MT (106 +/- 2 nmol Cd bound/g) than starvation (Zn = 405 +/- 21, MT = 9 +/- 3) in MT+/+ mice after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed. When uninduced, typically during Zn deficiency, MT appears to conserve Zn and body mass by reducing only urinary and other nonintestinal Zn losses.

Topics: Animals; Body Composition; Enteritis; Feces; Food Deprivation; Intestinal Mucosa; Intestines; Lipopolysaccharides; Liver; Metallothionein; Mice; Starvation; Water-Electrolyte Balance; Weight Loss; Zinc

Metallothioneins (MTs) occur throughout the animal kingdom and they are induced in vivo by metals, hormones, cytotoxic agents, and some kind of stress. It is well known that various stresses such as starvation and immobilization can induce MT synthesis in animal tissues, but the influence of dietary restriction is unknown. The MT levels in the liver increased by food-deprivation and then decreased by refeeding, and a long period of starvation down-alters hepatic MT levels. When the stress is intensified, the induced quantity of hepatic MT is reduced. It became clear that hepatic MT concentrations are controlled within a two fold limit when stressed by dietary restriction. MT was also induced in rat liver at recovery stage following an exhaustive running exercise, and thionein was synthesized first and then zinc bound to the protein. The half-life of hepatic MT induced by exercise (which is a nonmetallic inducer) was estimated at 5.2 h. Preinduced MT markedly suppressed exercise-induced lipid peroxidation in rat liver.

Topics: Animals; Energy Intake; Lipid Peroxidation; Liver; Male; Metallothionein; Physical Conditioning, Animal; Rats; Rats, Wistar; Starvation

A cDNA from metallothionein (MT) messenger RNA was identified in a library representing mRNA transcripts that are abundant in starving Atlantic cod larvae. The cod MT cDNA is closely related to MT mRNAs from other fish species and codes for a predicted 60 amino acid peptide. In adult cod liver MT mRNA is abundant and it is detected in cod eggs and larvae. Levels of MT mRNA were four times higher in three-week-old cod larvae starved for six days than in fed larvae, while starvation of four-week-old larvae for eight days resulted in a nearly seven-fold elevation in MT mRNA levels.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA, Complementary; Fishes; Gene Expression; Metallothionein; Molecular Sequence Data; RNA, Messenger; Sequence Homology, Amino Acid; Starvation

Eighteen hours of immobilization stress, accompanied by food and water deprivation, increased liver metallothionein (MT) but decreased kidney MT levels. Food and water deprivation alone had a significant effect only on liver MT levels. In contrast, stress and food and water deprivation increased both liver and kidney lipid peroxidation levels, indicating that the relationship between MT and lipid peroxidation levels (an index of free radical production) is unclear. Adrenalectomy increased both liver and kidney MT levels in basal conditions, whereas the administration of corticosterone in the drinking water completely reversed the effect of adrenalectomy, indicating an inhibitory role of glucocorticoids on MT regulation in both tissues. Changes in glutathione (GSH) metabolism produced significant effects on kidney MT levels. Thus, the administration of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased kidney GSH and increased kidney MT content, suggesting that increased cysteine pools because of decreased GSH synthesis might increase kidney MT levels through an undetermined mechanism as it appears to be the case in the liver. However, attempts to increase kidney MT levels by the administration of cysteine or GSH were unsuccessful, in contrast to what is known for the liver. The present results suggest that there are similarities but also substantial differences between liver and kidney MT regulation in these experimental conditions.

Topics: Adrenal Glands; Adrenalectomy; Animals; Buthionine Sulfoximine; Corticosterone; Glutathione; Isoxazoles; Kidney; Liver; Male; Metallothionein; Methionine Sulfoximine; Organ Specificity; Rats; Rats, Sprague-Dawley; Restraint, Physical; Starvation; Stress, Physiological

The distribution of metallothionein-I (MT) in several areas of the brain and its induction by immobilization stress has been studied in the rat. MT content was highest in hippocampus and midbrain and lowest in frontal cortex and pons plus medulla oblongata. Immobilization stress for 18 hours (which was accompanied by food and water deprivation) significantly increased MT levels in the frontal cortex, pons plus medulla oblongata and hypothalamus, but not in midbrain and hippocampus. The effect of stress on MT levels was specific as food and water deprivation along had no significant effect on MT levels in any of the brain areas studied. The effect of stress on MT levels was independent of changes in cytosolic Zn content; this was generally unaffected by stress or food and water deprivation but decreased in pons plus medulla oblongata from stressed rats. The results suggest that MT is induced more significantly in the brain areas that are usually involved in the response of animals to stress.

Topics: Analysis of Variance; Animals; Brain; Cytosol; Male; Metallothionein; Organ Specificity; Rats; Rats, Inbred Strains; Reference Values; Restraint, Physical; Starvation; Stress, Psychological; Zinc

Stress and starvation increased liver metallothionein (MT) and decreased liver glutathione (GSH) levels. Serum cysteine plus cystine levels were increased by stress. The exogenous administration of GSH, while not modifying hepatic GSH content, increased liver MT levels in basal and starved rats but not in stressed rats. Liver and serum cysteine levels were increased by GSH administration, a process partially reverted by the irreversible inhibitor of gamma-glutamyl transpeptidase, alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid. Mouse and rat liver MT levels were also increased by buthionine sulfoximine, an inhibitor of GSH synthesis, indicating that GSH is not a necessary precursor of MT. In addition, the hepatic MT content was increased by the administration of cysteine in a dose-response manner. These results suggest that hepatic MT synthesis is elevated by increased cysteine pools, and that MT, GSH and cysteine levels are somehow inter-related. MT, besides GSH, may be contemplated as a putative intracellular reservoir of cysteine in the liver of adult rats.

Topics: Animals; Body Weight; Buthionine Sulfoximine; Cysteine; Glutathione; Isoxazoles; Liver; Male; Metallothionein; Methionine Sulfoximine; Organ Size; Rats; Rats, Inbred Strains; Starvation; Stress, Physiological; Zinc

The effects of starvation and refeeding of 2-wk-old turkey poults on serum and tissue levels of zinc, copper and iron were investigated. Serum concentrations of zinc and copper declined during 4 d of starvation. Refeeding for 24 h following a period of starvation restored serum copper to levels similar to those in the fed controls but failed to elevate zinc levels. Liver concentrations and total quantities of zinc, copper and iron increased throughout starvation. Refeeding the starved poults reduced hepatic metal concentrations but caused a further increase in total metal content. This was apparently related to the large increase in liver mass, and the effect was most pronounced in poults starved 1 d prior to refeeding. Starvation also caused an increased zinc concentration and content and a reduced copper content in the pancreas, duodenal mucosa and kidney. Iron content of the pancreas and kidney increased during starvation, but that of the duodenal mucosa declined. Starvation evoked a progressive increase in the cytosolic zinc concentration from liver, pancreas, duodenal mucosa and kidney. A major part of this increase was accounted for as zinc bound to metallothionein (MT). Refeeding rapidly reduced cytosolic and MT-bound zinc in each of these tissues. It was concluded that starvation and refeeding had major effects on tissue trace metal status. A function is proposed for MT during starvation as a mechanism for the conservation of body zinc stores. Zinc, released as a consequence of tissue catabolism, is repartitioned into a soluble storage site (MT), which can be rapidly mobilized to meet the demands of new tissue synthesis once anabolic metabolism resumes.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Copper; Cytosol; Female; Food; Iron; Male; Metallothionein; Organ Size; Poultry Diseases; Starvation; Tissue Distribution; Turkeys; Zinc

These studies were designed to investigate the effects of stress and of changes in zinc status on plasma and liver concentrations of metallothionein-I (MT-I) in rats and to assess the value of plasma MT-I assays in the diagnosis of zinc deficiency. No MT-I was detected by radioimmunoassay in the plasma or liver of rats made hypozincaemic by feeding diets with less than 1 or 3 mg Zn/kg. Injection of normal rats with endotoxin or CCl4 also decreased plasma zinc levels, but these treatments greatly increased MT-I concentrations in both liver and plasma. Moreover plasma MT-I levels in zinc-deprived rats given endotoxin were only slightly greater than those in untreated rats of normal zinc status. Neither plasma zinc nor MT-I levels were altered in starved rats despite increased levels of the protein in the liver, although a slight increase in plasma MT-I was found in rats pair-fed with zinc-deficient animals. It appears therefore that reduced plasma levels of both zinc and MT-I are indicative of a zinc deficiency state and that assay of plasma MT should be of value in the diagnosis of zinc deficiency.

Topics: Animals; Carbon Tetrachloride Poisoning; Endotoxins; Liver; Male; Metallothionein; Protein Deficiency; Rats; Starvation; Stress, Physiological; Zinc

Parenchymal and non-parenchymal cells were isolated from the livers of control, starved, Zn2+-injected and Cd2+-injected rats. Parenchymal cells were prepared by differential centrifugation after perfusion of the liver with collagenase. Non-parenchymal cells were separated from parenchymal cells by unit-gravity sedimentation and differential centrifugation. Yields of 2 x 10(8) non-parenchymal cells with greater than 95% viability and less than 0.2% contamination with parenchymal cells were obtained without exposing cells to Pronase. Metallothioneins-I and -II were identified in parenchymal cells and non-parenchymal cells from Zn2+-treated rats. The metallothionein contents of parenchymal cells, non-parenchymal cells and intact liver were quantified by a competitive 203Hg-binding assay. Administration of heavy-metal salts significantly increased the metallothionein content of both cell populations, although the concentration of the protein was approx. 2.5-fold greater in parenchymal cells than in non-parenchymal cells. Overnight starvation increased the metallothionein content of parenchymal cells without altering that of non-parenchymal cells. The potential significance of this differential response by different liver cell types with regard to the influence of Zn2+ on stress-mediated alterations in hepatic metabolism is discussed.

Topics: Animals; Cadmium; Cell Separation; Chromatography, Ion Exchange; Liver; Male; Metalloproteins; Metallothionein; Rats; Rats, Inbred Strains; Starvation; Zinc