In vivo effects of cadmium on rat liver glucocorticoid receptor functional properties

Dunđerski, Jadranka; Stanošević, J.; Ristić, Biljana; Trajković, Divna; Matić, Gordana

doi:10.1016/0020-711x(92)90375-b

Cited by 14 publications

(5 citation statements)

References 30 publications

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“…This effect of heat stress coincided with decrease in the amount of GR protein in the cytosolic fraction and its increase in the nuclei, whereas the total cellular concentration of the receptor seemed to remain unchanged. Similar reduction of the glucocorticoid binding capacity and GR protein level in the cytosol was observed during chemical stresses, such as cadmium or arsenite intoxication (Simons et al, 1990;Dunđerski et al, 1992).…”

Section: Discussionsupporting

confidence: 61%

“…In contrast to studies on cells grown in culture, in vivo studies on the effects of stress on steroid receptor action have remained limited. Results from our laboratory showed that both 41°C whole-body hyperthermic stress (Matić et al, 1989(Matić et al, , 1995 and intoxication by heavy metals (Dunđerski et al, 1992) cause a considerable reduction of rat liver GR hormone-binding capacity, which could rather be attributed to stimulated nuclear import of the receptor than to its faster degradation. Our previous immunoblot analyses of the GR in rat liver revealed a significant decrease in its cytoplasmic level in response to both hyperthermic (Č voro et al, 1998) and chemical (Dunđerski et al, 2000;Brkljačić et al, 2004) stress.…”

Section: Introductionmentioning

confidence: 89%

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Alteration of glucocorticoid receptor subcellular distribution by hyperthermic stress

Čvoro

Korać²,

Matić

2006

ARCH BIOL SCI BELGRA

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The aim of the present study was to examine intracellular redistribution of the glucocorticoid receptor (GR) in rat liver cells during a 24-h time period after exposure of the animals to 41°C whole body hyperthermic stress. The level of the receptor protein in the cytoplasmic and nuclear compartments was measured by immunoblotting procedures applied to both crude cytosol and immunopurified GR, as well as by immunocytochemical analyses applied to both paraffin-embedded liver sections and unfixed nuclear smears. All the experimental approaches employed in the study provided similar results, demonstrating that the transient stress-related decline of the cytoplasmic GR observed during the first five hours after exposure of the animals to whole-body hyperthermic stress is accompanied by enhanced nuclear accumulation of the receptor. The study can contribute to a better understanding of the influence of stress on the glucocorticoid signal transduction pathway.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 89%

Alteration of glucocorticoid receptor subcellular distribution by hyperthermic stress

Čvoro

Korać²,

Matić

2006

ARCH BIOL SCI BELGRA

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“…It was found that heat stress applied to both cell cultures (Sanchez, 1992) and whole organisms (Matić et al, 1989) led to considerable loss of cytosolic GR binding capacity, that coincided with a reduction in GR protein in the cytosolic fraction (Č voro et al, 1998;Matić et al, 1995;Sanchez, 1992), and an increase in the nuclei (Matić et al, 1995;Sanchez, 1992). A similar reduction in steroid binding capacity of GR in the cytosol has been observed after chemical stresses, such as cadmium or arsenite toxicity (Dundjerski et al, 1992;Simons et al, 1990). However, there is a large variation in the extent of the reduction seen in these studies, and a clear correlation between the stress-related loss of GR protein from the cytosol and its accumulation in the nuclei is still lacking.…”

Section: Discussionmentioning

confidence: 58%

Immunocytochemical study of the glucocorticoid receptor in rat liver nuclei after hyperthermic stress

Čvoro¹

2003

Cell Biology International

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The presence of glucocorticoid receptors (GR) in rat liver nuclei over a 24 h time period following hyperthermic stress at 41 degrees C was immunocytologically studied using unfixed nuclear smears. Liver nuclei in unstressed animals were found to be immunonegative for GR. However, intense GR immunopositivity followed by a subsequent gradual decrease in receptor levels was observed in the nuclei of test animals during the first 2 h after stress. This stress-related increase in the receptor nuclear level was greater than the increase seen after dexamethasone administration. These results suggest that hyperthermic stress could potentiate the hormonal stimulation of receptor nuclear translocation.

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“…Like arsenic, cadmium exhibits a biphasic effect on GR function. Low doses reduce GR ligand binding capacity and inhibit GR-induction of the GR responsive MMTV promoter and the endogenous GR regulated gene TAT in rat liver [121,128]. However, higher doses enhance glucocorticoid activation of TAT [121].…”

Section: Effect Of Environmental and Chemical Toxins On Grmentioning

confidence: 99%

“…Other investigators have also shown that Cadmium (II) can inhibit steroid binding to GR [123,124]. The effects of this cadmium ion on GR appear to act through the redox state of the receptor as they can be reversed by the reducing agent dithiothreitol (DTT) [124,128]. Cadmium, like arsenite, binds to the vicinal dithiols in the ligand binding region of GR, thereby preventing ligand binding [124].…”

Section: Effect Of Environmental and Chemical Toxins On Grmentioning

confidence: 99%

The Glucocorticoid Receptor: A Revisited Target for Toxins

Marketon

Sternberg

2010

Toxins

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The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy.

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In vivo effects of cadmium on rat liver glucocorticoid receptor functional properties

Cited by 14 publications

References 30 publications

Alteration of glucocorticoid receptor subcellular distribution by hyperthermic stress

Alteration of glucocorticoid receptor subcellular distribution by hyperthermic stress

Immunocytochemical study of the glucocorticoid receptor in rat liver nuclei after hyperthermic stress

The Glucocorticoid Receptor: A Revisited Target for Toxins

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