Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins

Charalampopoulos, Ioannis; Tsatsanis, Christos; Dermitzaki, Eleni; Alexaki, Vasileia Ismini; Castanas, Elias; Margioris, Andrew N.; Gravanis, Achille

doi:10.1073/pnas.0306631101

Cited by 152 publications

(150 citation statements)

References 51 publications

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“…DHEA, DHEAS, and allopregnanolone also protect chromaffin cells and the sympathoadrenal PC12 cells against apoptosis induced by serum deprivation through mechanisms independent of NMDA and NOS inhibition (Charalampopoulos et al, 2005;Charalampopoulos et al, 2004). The effects of DHEA, DHEAS and allopregnanolone are time-and dose-dependent with EC 50 in the low nanomolar range.…”

Section: Anti-apoptosismentioning

confidence: 87%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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Section: Anti-apoptosismentioning

confidence: 87%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

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“…Our previous data, both in breast cancer cells (34) as well as on cells of different origin (PC12 pheochromocytoma cells; ref. 36), brain tissue (37), and prostate cancer (26,28,31,32), indicate that (a) steroid-specific antagonists do not modify the membrane binding characteristics of steroids, suggesting a different primary structure of the molecules (28,30,31); (b) saturation with high concentrations of steroids decreases the binding (37); and (c) BSA saturation decreases nonspecific binding of the protein-steroid conjugate on membranes (30). Based on these considerations, we advanced the above method for the tracing of membrane steroid receptors.…”

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Pelekanou

Kampa

Kafousi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for V90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxiainduced factor 1A, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007; 16(10):2016-23)

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“…Nuclear extracts of RAW 264.7 cells treated with the three peptides at 10 Ϫ8 M for 1 h were isolated as previously described (33,34). Briefly, cells were resuspended in a lysis buffer containing 0.6% Nonidet P-40, 10 mM HEPES, 10 mM KCl, 0.2 mM EDTA to extract the cytoplasmic proteins.…”

Section: Emsamentioning

confidence: 99%

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Tsatsanis¹,

Androulidaki²,

Alissafi³

et al. 2006

The Journal of Immunology

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Corticotropin-releasing factor (CRF) augments LPS-induced proinflammatory cytokine production from macrophages. The aim of the present study was to determine the mechanism by which CRF and its related peptides urocortins (UCN) 1 and 2 affect LPS-induced cytokine production. We examined their role on TLR4 expression, the signal-transducing receptor of LPS. For this purpose, the murine macrophage cell line RAW 264.7 and primary murine peritoneal macrophages were used. Exposure of peritoneal macrophages and RAW 264.7 cells to CRF, UCN1, or UCN2 up-regulated TLR4 mRNA and protein levels. To study whether that effect occurred at the transcriptional level, RAW 264.7 cells were transfected with a construct containing the proximal region of the TLR4 promoter linked to the luciferase gene. CRF peptides induced activation of the TLR4 promoter, an effect abolished upon mutation of a proximal PU.1-binding consensus or upon mutation of an AP-1-binding element. Indeed, all three peptides promoted PU.1 binding to the proximal PU.1 site and increased DNA-binding activity to the AP-1 site. The effects of CRF peptides were inhibited by the CRF2 antagonist anti-sauvagine-30, but not by the CRF1 antagonist antalarmin, suggesting that CRF peptides mediated the up-regulation of TLR4 via the CRF2 receptor. Finally, CRF peptides blocked the inhibitory effect of LPS on TLR4 expression. In conclusion, our data suggest that CRF peptides play an important role on macrophage function. They augment the effect of LPS by inducing Tlr4 gene expression, through CRF2, via activation of the transcription factors PU.1 and AP-1.

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Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins

Cited by 152 publications

References 51 publications

Neurosteroid regulation of central nervous system development

Neurosteroid regulation of central nervous system development

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

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