Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data are presented to show that ingestion of cadmium chloride by rats at low levels leads to alteration of zinc metabolism in the liver, even though the formation of metallothionein is not evident. A dose-response relationship between amount of cadmium ingested and degree of perturbation of zinc metabolism in liver was found. Oral cadmium was shown to cause emphysema and reduce pulmonary function in male rats; the effect was less severe or delayed in onset if dietary zinc concentration was high. Interference with copper and iron metabolism was shown to occur in rats given low levels of cadmium orally. Depression of copper and iron metabolism of the rat fetus was found to occur when dams received very low doses of cadmium during gestation, even though very little cadmium passed the placental barrier.
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PMID:Some effects of oral ingestion of cadmium on zinc, copper, and iron metabolism. 48 54

The transcription rates of the albumin and alpha-fetoprotein (alpha FP) genes were reduced to marginally detectable levels in livers of newborn or fetal c14CoS albino deletion mutant mice, which lack the hepatocyte specific developmental regulation (hsdr-1) locus on chromosome 7 and die shortly after birth. However, steady-state levels of these two mRNAs in livers of mutant mice were similar to those in normal mice, where these genes are actively transcribed. In c14CoS mice, transcription rates of transcription factor genes HNF-1, C/EBP and HNF-4 were reduced, albeit to different extents. These effects are specific because transcription of the HNF-3, DBP, LAP and Jun-B genes remained normal in mutant mice. Steady-state levels of all of these mRNAs reflected the transcriptional activities. Levels of HNF-1 and HNF-4 mRNAs showed much greater depression than that of C/EBP in mutant liver. The availability of this group of transcription factors may be reduced in c14CoS hepatocytes and therefore caused depressed transcription rates of their target genes such as those encoding albumin and alpha FP. However, the normal steady-state levels of albumin and alpha FP mRNAs in mutant mice remains unexplained. Fetal c14CoS hepatocytes in primary culture did acquire competence for glucocorticoid inducible transcription of the albumin, alpha FP, HNF-4 and metallothionein genes but not of the tyrosine aminotransferase (TAT) gene. These results indicate that the hsdr-1 locus is dispensable for the glucocorticoid induced transcription of these genes but not of TAT. The effects caused by the c14CoS deletion are pleiotropic in controlling the expression of numerous genes at distinct levels in the liver.
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PMID:Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice. 137 Dec 47

CRF is released in response to various stressors and regulates ACTH secretion and glucocorticoid production. CRF overproduction has been implicated in affective disorders, such as depression and anorexia nervosa, and may lead to Cushing's syndrome. To test whether CRF overproduction leads to Cushing's syndrome and to develop an animal model of chronic pituitary-adrenal activation, the CRF gene was expressed under control of the metallothionein promoter in transgenic mice. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. These animals display physical changes similar to those of patients with Cushing's syndrome, such as excess fat accumulation, muscle atrophy, thin skin, and alopecia. These findings indicate that chronic production of excess CRF results in sustained stimulation of pituitary corticotrope cells, resulting in elevated ACTH and consequent glucocorticoid overproduction, a condition that leads to the development of Cushing's syndrome. Analysis of CRF mRNA distribution revealed that transgene expression is primarily restricted to cells that express the endogenous CRF gene and does not follow the pattern predicted of a metallothionein-regulated gene. These results suggest that DNA elements located outside of the CRF promoter but present within the CRF intron, coding, or 3'-flanking regions may contribute to the cell type specificity of CRF gene expression.
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PMID:Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. 159 49

In 30- and 80-day-old LEC rats, hepatic Cu and Cu-metallothionein (MT) concentrations were much higher than those in control Fischer rats. The gross deposition was accompanied with enhancements of Zn and Fe concentrations. In LEC rats, more than half of the hepatic Cu was located in the cytosol fraction. Most of cytosolic Cu was bound to MT. In organs other than the liver, sharp depositions of Cu were not found. Both groups of LEC rats showed significantly low serum Cu concentrations and ceruloplasmin activity. The great accumulation of hepatic Cu with the increase of age is due to the inherent depression of the release of Cu from the liver. The deposition may be closely related to the onset of the sudden hepatitis observed in LEC rats.
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PMID:Copper metabolism in LEC rats aged 30 and 80 days old: induction of Cu-metallothionein and status of zinc and iron. 194 38

The human cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids among lipoproteins. In order to evaluate the effects of increased plasma CETP on lipoprotein levels, a human CETP minigene was placed under the control of the mouse metallothionein-I promoter and used to develop transgenic mice. Integration of the human CETP transgene into the mouse genome resulted in the production of active plasma CETP. Zinc induction of CETP transgene expression caused depression of serum cholesterol due to a significant reduction of high density lipoprotein cholesterol. There was no change in total cholesterol content in very low and low density lipoproteins. However, there was a decrease in the free cholesterol/cholesteryl ester ratio in plasma and in all lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of plasma cholesterol esterification. The results suggest that high levels of plasma CETP activity may be a cause of reduced high density lipoproteins in humans.
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PMID:Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. 204 May 99

The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status.
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PMID:Iron-induced metallothionein in chick liver: a rapid, route-dependent effect independent of zinc status. 221 49

The purpose of this 2 factorial designed study was to investigate the influence of citric acid on the availability of zinc from diets containing 140 g corn germs as a native phytate source (0.5% phytate in diet). Growing male rats with an average initial weight of 42 g were divided into 8 groups of 8 animals each. After a 7 d depletion period (2.4 micrograms Zn/g diet) the animals were fed ad libitum for 21 d a diet on the basis of egg white solid and corn germs. The diets were supplemented with zinc in order to obtain phytate:zinc molar ratios of 31, 20, 14, and 0 (control without corn germs, 11 micrograms Zn/g diet). Each diet was fed with and without a supplementation of 1% citric acid. A phytate:Zn molar ratio of 31:1 resulted in typical symptoms of zinc-deficiency like anorexia, alopecia and a significant depression of growth. These effects were apparently reduced by citric acid. The zinc concentration in serum and organs followed the graded levels of phytate:zinc molar ratios. Primary significant effects of the phytate:Zn molar ratio but also effects of citric acid and interactions between the 2 factors phytate:Zn and citric acid could be detected. Only total liver zinc but not liver zinc based on fresh matter was affected by the phytate:Zn molar ratio. In serum and tissues the activity of alkaline phosphatase showed a significant response to the phytate:zinc molar ratio. Furthermore the supplementation with citric acid increased the femur alkaline phosphatase and slightly reduced it in the liver. The concentrations of metallothionein in liver duodenum, jejunum and ileum were significantly affected by the phytate:Zn molar ratio.
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PMID:[The effect of a supplement of citric acid on the bioavailability of zinc from corn germ]. 233 19

Interleukin 1 (IL 1) production is stimulated by infection, cellular injury, and inflammation. This cytokine directs a wide spectrum of host responses. Human interleukin 1 alpha (IL 1 alpha) was used to examine the time course of effects on zinc metabolism as part of the acute phase response. IL 1 produced a transient depression in the serum zinc concentration and increased serum ceruloplasmin. Metallothionein levels were increased in liver 14-fold after IL 1. Increased expression of metallothionein-1 and -2 genes following IL 1 were observed in liver, bone marrow, and thymus. Pulse-labeling experiments with i.v.-administered 65Zn showed that IL 1 drastically altered zinc distribution kinetics among tissues. More 65Zn was taken up (and/or retained) by the liver, bone marrow, and thymus 6 h after IL 1, whereas correspondingly less 65Zn was found in bone, skin, and intestine. Uptake by other tissues was not affected by IL 1. Chromatography of cytosol from tissues with increased 65Zn uptake suggests the IL 1-induced redistribution may be driven by enhanced metallothionein synthesis. Collectively, the results show that IL 1 regulates zinc metabolism and may direct its preferential, tissue-specific distribution via elevated metallothionein-1 and -2 gene expression.
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PMID:Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. 245 83

Regulation of zinc metabolism by dibutyryl cAMP, glucagon, and epinephrine was examined in rats fed adequate amounts of zinc. Dibutyryl cAMP, epinephrine, and glucagon each produced an increase in liver metallothionein levels by 10 h after they were first administered. The increase in liver metallothionein was inversely related to the serum zinc concentration. Treatment with dexamethasone, a glucocorticoid, accentuated these effects to some extent. Both metallothionein I and II were induced by dibutyryl cAMP and glucagon. Levels of metallothionein mRNA in total liver RNA extracts were measured by dot blot hybridization using a synthetic 21-base oligonucleotide complimentary to the 5' region of both the metallothionein I and II genes. Individual administration of dibutyryl cAMP, glucagon, and epinephrine increased the number of metallothionein mRNA molecules per cell by up to fourfold. The data suggest that glucagon and epinephrine are primary regulators of metallothionein gene expression acting at least in part via cAMP. In adrenalectomized rats, glucagon, dibutyryl cAMP, and epinephrine had a less potent effect in terms of metallothionein induction and depression of serum zinc concentrations. These effects were largely restored when dexamethasone was also given. Collectively these data suggest that changes in zinc metabolism associated with acute stress involve coordinate regulation mediated by many factors, including glucocorticoids and cAMP.
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PMID:Coordinate regulation of zinc metabolism and metallothionein gene expression in rats. 302 99

Retrovirus vectors [direct orientation (DO) vectors] that permit the simultaneous expression of an inserted protein-coding sequence and a dominant-acting selectable marker have been constructed. In these vectors, an internal simian virus 40 or human metallothionein promoter sequence serves to drive the expression of the bacterial neomycin phosphotransferase or guanine-xanthine phosphoribosyltransferase genes, whereas the viral long terminal repeat sequences are utilized to promote expression of inserted sequences. In some of the vectors, the viral 5' splice site, normally used in the biogenesis of the subgenomic env-encoding mRNA, has been eliminated. These vectors yield high transient and stable titers of virus after transfection of viral packaging cell lines, show little or no depression of virus titer with a variety of inserts, and faithfully transmit recombinant proviral sequences to recipient cells. To characterize the expression potential of these vectors, a variety of inserts encoding the alpha and beta subunits of the human major histocompatibility complex class II antigen HLA-DR have been introduced into these vectors. NIH 3T3 cells infected by viruses containing HLA-DR alpha or beta cDNAs express these proteins as shown by immunoprecipitation of metabolically labeled extracts. In addition, through the sequential infection of cells with retrovirus constructions expressing two different selectable markers, both subunits of the class II antigen have been introduced into NIH 3T3 cells. Such infected cells express HLA-DR molecules at the cell surface.
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PMID:Expression of human class II major histocompatibility complex antigens using retrovirus vectors. 303 67


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