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Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence

Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopoly...

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Autores principales: Racchi, Marco, Buoso, Erica, Ronfani, Melania, Serafini, Melania M., Galasso, Marilisa, Lanni, Cristina, Corsini, Emanuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535944/
https://www.ncbi.nlm.nih.gov/pubmed/28684670
http://dx.doi.org/10.3390/ijms18071453
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author Racchi, Marco
Buoso, Erica
Ronfani, Melania
Serafini, Melania M.
Galasso, Marilisa
Lanni, Cristina
Corsini, Emanuela
author_facet Racchi, Marco
Buoso, Erica
Ronfani, Melania
Serafini, Melania M.
Galasso, Marilisa
Lanni, Cristina
Corsini, Emanuela
author_sort Racchi, Marco
collection PubMed
description Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence.
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spelling pubmed-55359442017-08-04 Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence Racchi, Marco Buoso, Erica Ronfani, Melania Serafini, Melania M. Galasso, Marilisa Lanni, Cristina Corsini, Emanuela Int J Mol Sci Review Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence. MDPI 2017-07-06 /pmc/articles/PMC5535944/ /pubmed/28684670 http://dx.doi.org/10.3390/ijms18071453 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Racchi, Marco
Buoso, Erica
Ronfani, Melania
Serafini, Melania M.
Galasso, Marilisa
Lanni, Cristina
Corsini, Emanuela
Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title_full Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title_fullStr Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title_full_unstemmed Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title_short Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
title_sort role of hormones in the regulation of rack1 expression as a signaling checkpoint in immunosenescence
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535944/
https://www.ncbi.nlm.nih.gov/pubmed/28684670
http://dx.doi.org/10.3390/ijms18071453
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