Inhibition of Heat Shock Transcription Factor by GR

Wadekar, Subhagya A.; Li, Dapei; Periyasamy, Sumudra; Sánchez, Edwin R.

doi:10.1210/mend.15.8.0674

Cited by 33 publications

(17 citation statements)

References 53 publications

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“…On the contrary, Hsp90 gene was upregulated by cortisol and then downregulated through the synthesized protein. In both cases a negative feedback mechanism could be invoked [45]. In other fish species, similar results have been reported [29,35] and it has been shown a quick time (15-90 min) for Hsp70 mRNA transcription [17] Differences in cortisol Hsp modulation reported in the literature [1,12,43] could be dependent on the organ and cell types examined in various fish species and/or by the experimental conditions.…”

Section: Discussionsupporting

confidence: 56%

Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea bass head kidney and isolated leukocytes

Celi

Vazzana

Sanfratello

et al. 2012

General and Comparative Endocrinology

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In fish, interactions between Hsps and cortisol are involved in stress modulated physiological processes including innate immune responses. Cortisol exerts a role in the regulation of Hsps synthesis. Fish head kidney is a lymphomieloid and endocrine organ releasing cortisol, and it is the central organ for immune-endocrine interactions. In sea bass, cortisol intraperitoneal injection and in vitro treatment of head kidney cells show that inducible Hsp70 and Hsp90 are modulated by this hormone. However, an inverse relationship between mRNA expression (real-time PCR) and Hsp70 and Hsp90 protein levels (densitometric band analysis) was found. Time-course assays indicate a cortisol-mediated regulation. Furthermore, Hsp70 gene modulation appears to be more susceptible to the cortisol action and the mRNA was transcribed within 3h post-injection. The restoration of the homeostatic conditions was observed at a week p.i., when plasma cortisol baseline was reached. Although fish manipulation and injection exerted stressing effects as indicated by serological parameters, differences between cortisol treated specimens compared to untreated or sham fish are statistically significant. Similar results were found by examining in vitro total cells and isolated leukocytes from head kidney cultured for 3h with increasing cortisol concentration. Finally, MTT test and DNA fragmentation experiments showed that the apoptotic effect expected in cortisol-treated cells could be counteracted by high Hsp70 intracellular levels.

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Section: Discussionsupporting

confidence: 56%

Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea bass head kidney and isolated leukocytes

Celi

Vazzana

Sanfratello

et al. 2012

General and Comparative Endocrinology

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“…The in situ localization experiments in C. elegans described in the present paper demonstrate that DAF-21 is both a constitutive and a heatinduced protein. A recent study has shown that the major HSP (HSP70, 90 and 110) incur heat shock response through binding to heat shock factor-1 and that glucocorticoids regulate signaling (Wadekar et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Caenorhabditis elegans DAF‐21 (HSP90) is characteristically and predominantly expressed in germline cells: Spatial and temporal analysis

Inoue

Takamura

Yamae³

et al. 2003

Dev Growth Differ

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Three monoclonal antibodies against antigens that exist in the Caenorhabditis elegans germ line have previously been described. In the present study, a full-length mRNA for one of these antigens was isolated, and by sequencing its corresponding cDNA, it was predicted that the protein would show a high homology with the 90 kDa heat shock protein (HSP90) in other species, and with the protein of daf-21 , a previously identified hsp90 homologue. The spatial and temporal distribution of the antigen (DAF-21) was analyzed in C. elegans , and the localization of daf-21 mRNA, as detected by in situ hybridization, agreed with that detected by the monoclonal antibody. Under normal conditions, daf-21 mRNA is characteristically distributed in postembryonic germ cells derived from Z2 and Z3 cells in both hermaphrodites and males. Under heat stress conditions, however, daf-21 mRNA was not only detected in germ cells, but also apparently expressed all over the body. In addition, the DAF-21 protein seemed to be localized in the perinuclear region of somatic cells.

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“…Transfer of the samples to Immobilon-P ® membranes (Millipore Corp.) and quantitative immunoblotting were performed as described previously (8,11). The BuGR2 monoclonal antibody against GR (Affinity Bioreagents) was used to probe for receptor, and various antibodies were used to probe for Hsp90 (H38220, Transduction Laboratories, Inc.), FKBP52 (UPJ56 (12)), FKBP51 (PA0-021, Affinity Bioreagents), and dynein intermediate chain (monoclonal antibody 1618, Chemicon International, Inc.).…”

Section: Methodsmentioning

confidence: 99%

A New First Step in Activation of Steroid Receptors

Davies

Ning

Sánchez

2002

Journal of Biological Chemistry

Self Cite

373

137

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We have identified a new first step in the hormonal activation of the glucocorticoid receptor (GR). Rather than causing immediate dissociation of the cytoplasmic GR heterocomplex, binding of hormone-induced substitution of one immunophilin (FKBP51) for another (FKBP52), and concomitant recruitment of the transport protein dynein while leaving Hsp90 unchanged. Immunofluorescence and fractionation revealed hormone-induced translocation of the hormone-generated GR⅐Hsp90⅐FKBP52⅐dynein complex from cytoplasm to nucleus, a step that precedes dissociation of the complex within the nucleus and conversion of GR to the DNAbinding form. Taken as a whole, these studies identify immunophilin interchange as the earliest known event in steroid receptor signaling and provide the first evidence of differential roles for FKBP51 and FKBP52 immunophilins in the control of steroid receptor subcellular localization and transport. The glucocorticoid receptor (GR)1 is a hormone-activated transcription factor that requires hormonally driven movement to its site of action within the nucleus. In the absence of hormone, the GR is recovered in the cytosolic fraction of cells as an oligomeric complex containing one molecule of receptor and two molecules of heat shock protein 90 (Hsp90), to which the receptor binds directly (for review see Ref. 1). An intriguing recent development, however, is that hormone-free receptor is not found as a single, well defined complex but exists as a mixture of complexes. Although all of these complexes contain receptor and Hsp90, each contains only one molecule of either FKBP52, FKBP51, Cyp40, or PP5. The latter proteins have been classified as TPR domain proteins based on the presence of several tetratricopeptide repeat domains that are their sites of interaction with Hsp90 (2, 3). FKBP52, FKBP51, and Cyp40 are also members of the immunophilin family of proteins (4 -6). Thus, it is now clear that up to four distinct receptor heterocomplexes are possible, even within the same cell or tissue; yet almost nothing is known about the differential roles served by each immunophilin in steroid receptor responses.It is generally accepted that the first event in hormonal activation of GR is dissociation of hormone-bound GR from Hsp90 and the TPR proteins, followed by nuclear translocation of the GR and all other downstream events. Hormone-induced dissociation of the complex is a rapid event, occurring both in the intact cell (7) and in cytosolic preparations (8). In cytosols, dissociation of GR complexes has been shown to require warming (typically 20 -25°C) in addition to hormone, and this process can be blocked by molybdate and other transition metal oxyanions (8, 9). Indeed, because of the ability of molybdate to effectively block dissociation, it has been assumed that molybdate-stabilized receptors are more or less "frozen" in their native, untransformed state even when GR is bound with hormone. In this work, we have examined this assumption by measuring the effect of hormone on the immunophilin content of GR hetero...

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Inhibition of Heat Shock Transcription Factor by GR

Cited by 33 publications

References 53 publications

Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea bass head kidney and isolated leukocytes

Elevated cortisol modulates Hsp70 and Hsp90 gene expression and protein in sea bass head kidney and isolated leukocytes

Caenorhabditis elegans DAF‐21 (HSP90) is characteristically and predominantly expressed in germline cells: Spatial and temporal analysis

A New First Step in Activation of Steroid Receptors

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