scholarly journals Impact of selenite and selenate on differentially expressed genes in rat liver examined by microarray analysis

2010 ◽  
Vol 30 (5) ◽  
pp. 293-306 ◽  
Author(s):  
Astrid C. Bosse ◽  
Josef Pallauf ◽  
Bettina Hommel ◽  
Mariana Sturm ◽  
Susanne Fischer ◽  
...  

Sodium selenite and sodium selenate are approved inorganic Se (selenium) compounds in human and animal nutrition serving as precursors for selenoprotein synthesis. In recent years, numerous additional biological effects over and above their functions in selenoproteins have been reported. For greater insight into these effects, our present study examined the influence of selenite and selenate on the differential expression of genes encoding non-selenoproteins in the rat liver using microarray technology. Five groups of nine growing male rats were fed with an Se-deficient diet or diets supplemented with 0.20 or 1.0 mg of Se/kg as sodium selenite or sodium selenate for 8 weeks. Genes that were more than 2.5-fold up- or down-regulated by selenite or selenate compared with Se deficiency were selected. GPx1 (glutathione peroxidase 1) was up-regulated 5.5-fold by both Se compounds, whereas GPx4 was up-regulated by only 1.4-fold. Selenite and selenate down-regulated three phase II enzymes. Despite the regulation of many other genes in an analogous manner, frequently only selenate changed the expression of these genes significantly. In particular, genes involved in the regulation of the cell cycle, apoptosis, intermediary metabolism and those involved in Se-deficiency disorders were more strongly influenced by selenate. The comparison of selenite- and selenate-regulated genes revealed that selenate may have additional functions in the protection of the liver, and that it may be more active in metabolic regulation. In our opinion the more pronounced influence of selenate compared with selenite on differential gene expression results from fundamental differences in the metabolism of these two Se compounds.

2012 ◽  
Vol 109 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Megumi Kotani ◽  
Ki Hyun Kim ◽  
Natsumi Ishizaki ◽  
Masayuki Funaba ◽  
Tohru Matsui

Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.


1987 ◽  
Vol 57 (3) ◽  
pp. 319-329 ◽  
Author(s):  
Marja Mutanen ◽  
Pekka Koivistoinen ◽  
Virginia C. Morris ◽  
Orville A. Levander

1. A Finnish national programme to fertilize crops with sodium selenate led us to compare the nutritional availability to rats of selenium in two Finnish spring wheats (Triticum aestivum L.), either fertilized or sprayed with sodium selenate, with that in an American winter bread wheat naturally high in Se.2. Weanling male rats were given a Se-deficient Torula yeast diet for 4 weeks followed by either continued depletion or repletion for 4 weeks with graded levels of Se as sodium selenite (standard) or wheat (test food). Plasma and liver Se levels and plasma and liver glutathione peroxidase (EC 1.11.1.9; GSH-Px) activities were used as criteria of body Se status.3. The availability of Se under these conditions was calculated with the point-slope technique at two dietary levels of Se (Expt 1) and with the slope-ratio method (Expt 2).4. In the point-slope assay, the level of dietary Se fed had a considerable effect on the apparent availability values obtained which made interpretation of the results difficult. In the slope-ratio assay, no difference in the availability of Se from the various wheats was observed when plasma or liver Se levels were used as the response criteria.5. The Se in the fertilized wheat was somewhat more available than that in the sprayed wheat when plasma or liver GSH-Px activities were the response criteria. Overall, availability values (% ) derived by averaging all four response criteria were 86, 77 and 73 for the fertilized and sprayed Finnish wheats and the American wheat respectively (sodium selenite 100).6. These results show that wheat is a relatively available source of Se to rats regardless of whether its Se content is naturally high or is increased by fertilization or spraying.


1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.


1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.


1990 ◽  
Vol 5 (3) ◽  
pp. 267-274 ◽  
Author(s):  
I. Porsch Hällstöm ◽  
J.-Å. Gustafsson ◽  
A. Blanck

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.


2009 ◽  
Vol 181 (3) ◽  
pp. 400-408 ◽  
Author(s):  
Felipe Samuel Pessoto ◽  
Natalia Mayumi Inada ◽  
Maria de Fátima Nepomuceno ◽  
Ana Célia Ruggiero ◽  
Otaciro R. Nascimento ◽  
...  

1997 ◽  
Vol 61 (1) ◽  
pp. 17-32
Author(s):  
G A Marzluf

In the fungi, nitrogen metabolism is controlled by a complex genetic regulatory circuit which ensures the preferential use of primary nitrogen sources and also confers the ability to use many different secondary nitrogen sources when appropriate. Most structural genes encoding nitrogen catabolic enzymes are subject to nitrogen catabolite repression, mediated by positive-acting transcription factors of the GATA family of proteins. However, certain GATA family members, such as the yeast DAL80 factor, act negatively to repress gene expression. Selective expression of the genes which encode enzymes for the metabolism of secondary nitrogen sources is often achieved by induction, mediated by pathway-specific factors, many of which have a GAL4-like C6/Zn2 DNA binding domain. Regulation within the nitrogen circuit also involves specific protein-protein interactions, as exemplified by the specific binding of the negative-acting NMR protein with the positive-acting NIT2 protein of Neurospora crassa. Nitrogen metabolic regulation appears to play a significant role in the pathogenicity of certain animal and plant fungal pathogens.


1958 ◽  
Vol 4 (6) ◽  
pp. 771-776 ◽  
Author(s):  
Mary L. Petermann ◽  
Mary G. Hamilton

Rat liver was homogenized in 0.88 M sucrose. The DNA and total RNA were determined, and the homogenate was fractionated by differential centrifugation. The pellets obtained between 30 minutes at 20,000 g and 180 minutes at 105,000 g were analyzed for RNA and nitrogen. The ribonucleoproteins were determined in the analytical ultracentrifuge. The non-pellet RNA was calculated by difference. The results are reported as amounts per 6.7 x 10-9 mg. of DNA. In young, growing male rats the amounts of microsomal protein and ribonucleoprotein B (83S) increased with age. Non-pregnant adult females showed less non-pellet RNA and much more ribonucleoprotein C (63S) than did adult males. During pregnancy both of these cell constituents reverted to levels characteristic for male animals. Starvation for 5 days resulted in a reduction in the mass of liver tissue, the non-pellet RNA, the microsomal protein, and ribonucleoproteins B and C. During recovery from starvation the return of the liver to normal paralleled the rate at which body weight was restored. Treatment with cortisone, 25 mg. per rat per day for 5 days, caused an increase in microsomal protein and a decrease in ribonucleoprotein B. Treatment with 6-mercapto-purine, 50 mg. per kilo per day for 5 days, caused little change in liver composition in either males or females.


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