Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression

Li, Da-Pei; Calzi, Sergio Li; Sánchez, Edwin R.

doi:10.1379/1466-1268(1999)004<0223:iohsfa>2.3.co;2

Cited by 24 publications

(12 citation statements)

References 41 publications

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“…Instead, vanadate treatment of LMCAT2 cells resulted in a dose-dependent potentiation of dexamethasone-induced pMMTV-CAT expression (Fig. 1A), with increased activity seen with vanadate ranging from 50 to 500 M. A potential explanation for this effect was that vanadate at these seemingly-high concentrations was actually a form of chemical shock, such as that seen with sodium arsenite, which we have previously shown will cause similar increases of GR activity in these same cells [21,22]. However, this mechanism was clearly not operating, as vanadate treatment (500 M) of L929 cells stably-transfected with an HSF1-responsive CAT reporter was found to inhibit heat and arsenite induction of HSF1 activity [15].…”

Section: Potentiation Of Gr-mediated Reporter Gene Expression By Sodimentioning

confidence: 66%

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Vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor

Calzi

Periyasamy

et al. 2002

The Journal of Steroid Biochemistry and Molecular Biology

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Transition metal oxyanions, such as molybdate, tungstate and vandadate, have been shown to prevent in vitro hormone-induced activation of the glucocorticoid receptor (GR) by blocking dissociation of the GR/heat shock protein heterocomplex. In this work, we report a novel effect of vanadate: in vivo potentiation of GR-mediated gene expression. In cells stably-transfected with complex (mouse mammary tumor virus (MMTV)) or minimal GR-regulated CAT reporters, treatment with 500 M vanadate caused CAT gene expression to dramatically increase, even at saturating concentrations of dexamethasone; while no such effect was seen in response to RU486 antagonist. Similar treatment with molybdate had no effect on GR activity, suggesting that the response to vanadate was not a general property of transition metal oxyanions. Treatment with vanadate after hormone-induced nuclear translocation of the GR also caused potentiation, demonstrating that vanadate was acting on a post-transformation event, perhaps by affecting the transactivation function of DNA-bound GR. Paradoxically, vanadate caused an apparent but temporary "loss" of GR protein immediately after treatment (as measured by loss of reactivity to BuGR2 antibody and of hormone-binding capacity) that returned to normal at approximately 8 h post-treatment, suggesting that potentiation of GR transactivation function (as measured by our CAT assays) was probably occurring during the later stages (8-24 h) of this assay. However, gel shift analyses revealed that vanadate could induce binding of the hormone-free GR to glucocorticoid response element (GRE)-containing oligonucleotides immediately after treatment. Thus, the rapid vanadate-induced "loss" of GR was not due to degradation of GR protein. Yet, vanadate in the absence of hormone had no effect on CAT reporter expression, demonstrating that this form of the GR still requires agonist for its enhanced transcriptional activity. As an indication of the potential mechanism of vanadate action, vanadate was found to dramatically stimulate the mitogen-activated protein kinases, ERK-1 and ERK-2. In addition, vanadate potentiation of GR reporter gene expression was completely blocked by the tyrosine kinase inhibitor herbimycin A. Taken as a whole, our results suggest that vanadate can have dramatic and complex effects on GR structure and function, resulting in hormone-free activation of GR DNA-binding function, as well as alterations to the BuGR2 epitope and hormone-binding domains-while at the same time stimulating tyrosine phosphorylation pathways controlling GR-mediated gene transcription.

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Section: Potentiation Of Gr-mediated Reporter Gene Expression By Sodimentioning

confidence: 66%

“…The various CAT reporter-expressing cells lines were established as previously described [21,22]. Briefly, mouse L929 cells were co-transfected with pSV2neo and a two-fold excess of pMMTV-CAT (LMCAT2 cells), or pGRE 2 E1B-CAT (LGRECAT cells) using lipofectin as carrier.…”

Section: Cell Culture and Vanadate Treatmentmentioning

confidence: 99%

Vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor

Calzi

Periyasamy

et al. 2002

The Journal of Steroid Biochemistry and Molecular Biology

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“…Cell Culture and Stress/Drug Treatment-The various CAT reporter-expressing cells lines were established as described previously (13,40). Briefly, mouse L929 cells were co-transfected with pSV2neo and a 2-fold excess of p2500-CAT (LHSECAT cells), pMMTV-CAT (LMCAT2 cells), or pGRE 2 E1B-CAT (LGEC cells) using Lipofectin as carrier.…”

Section: Methodsmentioning

confidence: 99%

“…7. Although this reporter typically yields a much smaller response to Dex than the MMTV promoter, the relative increase due to heat shock is much more dramatic with pGRE 2 E1B-CAT (13,40), making it look as if there is no response to Dex alone in Fig. 7.…”

Section: Sodium Vanadate Prevents the Stress Potentiation Of Gr Transmentioning

confidence: 99%

Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Periyasamy

Jones

et al. 2000

Journal of Biological Chemistry

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Heat shock and other forms of stress increase glucocorticoid receptor (GR) activity in cells, suggesting cross-talk between the heat shock and GR signal pathways. An unresolved question concerning this cross-talk is whether heat shock factor (HSF1) activity is required for this response. We addressed this issue by modulating HSF1 activity with compounds acting by distinct mechanisms: sodium vanadate (SV), an inhibitor of protein phosphatases; and wortmannin, an inhibitor of DNA-dependent protein kinase. Using HSF1-and GR-responsive CAT reporters, we demonstrate that SV inhibits both HSF1 activity and the stress potentiation of GR, while having no effect on the hormone-free GR or HSF1. Paradoxically, SV increased hormone-induced GR activity in the absence of stress. In contrast, wortmannin increased HSF1 activity in stressed cells and had no effect on HSF1 in the absence of stress. Using the pMMTV-CAT reporter containing the negative regulatory element 1 site for DNA-dependent protein kinase, wortmannin was found to increase the GR response. However, in cells expressing a minimal promoter lacking negative regulatory element 1 sites, wortmannin had no effect on the GR in the absence of stress but increased the stress potentiation of GR. Our results show that the mechanism by which GR activity is increased in stressed cells requires intrinsic HSF1 activity. The glucocorticoid receptor (GR)1 is a member of the nuclear receptor family of proteins that act as hormone-activated transcription factors (1, 2). Since the GR is known to be involved in the organismal response to stress (3), and since the hormonefree GR is known to reside in the cytoplasm as a complex containing heat shock proteins (HSPs) (4), we and others have investigated the role of the heat shock response in controlling GR function. Early evidence to suggest a relationship between these responses includes the ability of heat shock or chemical stress (arsenite) to cause nuclear translocation of hormone-free GR in mouse L929 and Chinese hamster ovary cells (5, 6) and a partial increase in GR-mediated gene expression in Chinese hamster ovary cells subjected to heat or chemical shock in the absence of hormone (6). Heat shock-induced nuclear translocation of hormone-free GR has also been documented in the liver of rats subjected to whole-body hyperthermia (7, 8) as well as in COS cells expressing human GR (9). Evidence to suggest that heat shock-induced nuclear translocation of hormone-free GR can result in altered expression of endogenous genes has also been accumulating. For example, heat shock treatment of COS and Hela cells in the absence of hormone results in GR-mediated transrepression of the collagenase promoter (9), while heat shock treatment of murine macrophages results in a pattern of Fc receptor expression or repression that is identical to that observed in response to hormone (10). More recently, heat shock-induced translocation of hormone-free GR has been implicated in the process of stress-induced apoptosis in leukemic cells (11).In the presenc...

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“…The xenobiotic response element (XRE) is localized in the promoter regions of several genes encoding proteins such as xenobiotic metabolizing enzymes 467 interaction influence XRE the regulation of gene expression. Flavonol quercetin has been reported to selectively inhibit GREdependent gene regulation [58].…”

Section: Impact On Genomicsmentioning

confidence: 99%

Bioactive substances of plant origin in food - impact on genomics

Orzechowski¹,

Ostaszewski²,

Jank³

et al. 2002

Reprod. Nutr. Dev.

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-In the past decade, substantial progress has been made concerning our knowledge of bioactive components in plant foods and their links to health. Human diets of plant origin contain many hundreds of compounds which cannot be considered as nutrients, but appear to play a role in the maintenance of health. These substances are called nutraceuticals. In some cases where the disease process is at least partially understood, elements of protection can be related to a single compound or structurally related group of compounds in the diet. Bioactive components of food which are of special interest include the following groups: polyphenols, phytoestrogens, phytosterols, phytates and polyunsaturated fatty acids. Most of them are featured by antioxidant properties. In the first part of this review, we indicate the main groups of bioactive compounds giving a description of their localisation, chemical properties and biological actions. Recently, it was shown, however, that the bioavailability of potential antioxidants from plant foods is generally too low to have any substantial direct effect on reactive oxygen species. As a result of that it is postulated that dietary compounds, even in very low concentrations, may have a far greater impact than previously appreciated on the regulation of gene expression. The second part of this paper concerns the action of the literally most important bioactive substances on the molecular mechanisms of the control of genes which in turn affect cellular metabolism. A few current studies on the action of selected nutraceuticals on the activity of transcription factors such as AP-1, NF-kB, SREBPs, PPARs as final targets in the signal transduction cascade and gene regulation are included. A detailed analysis of numerous factors of dietary origin with their targets is far beyond the scope of this paper. However, continuing research on the effects of nutraceuticals on gene expression should provide insight into the mechanisms of prevention of diseases such as obesity, diabetes, atherosclerosis, hypertension and cancer by dietary manipulations.bioactive compounds / antioxidants / transcription factors / AP-1 / NF-kB / PPARs / SREBPs / gene expression Reprod. Nutr. Dev. 42 (2002) [461][462][463][464][465][466][467][468][469][470][471][472][473][474][475][476][477] 461

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Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression

Cited by 24 publications

References 41 publications

Vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor

Vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor

Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Bioactive substances of plant origin in food - impact on genomics

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