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Role of Cortisol and Dehydroepiandrosterone on RACK1/PKC Signalling and Consequences in Immunosenescence

  • E. Buoso
  • Mm. Serafini
  • M. Galasso
  • M. Ronfani
  • L. Poloni
  • C. Lanni
  • E. Corsini
  • M. Racchi
Living reference work entry

Abstract

Over the past 15 years, it was demonstrated that defective protein kinase C (PKC) signal transduction machinery correlates to the decline of immune functions associated with aging. Experimental evidence suggest that altered PKC signalling results in impaired response to lipopolisaccaride (LPS) stimulation and cytokine release. Such defective signalling is due to reduced expression of receptor for activated C kinase 1 (RACK1) and to age-related alteration of the hormonal balance between cortisol and dehydroepiandrosterone (DHEA): cortisol levels remain substantially unchanged while DHEA levels decline with aging. These aspects are particularly relevant for the functional PKC signalling system because DHEA administration in vivo and in vitro in aged animals and in human cells can reestablish the levels of RACK1 and thus the function of the PKC signalling cascade. There is also evidence that cortisol and DHEA have opposite effect on the transcriptional regulation of the gene encoding for RACK1 and known as GNB2L1. At transcriptional level, cortisol has a peculiar function of a negative regulator of the RACK1 promoter, while the effect of DHEA seems to derive from a complex influence on the functions and post-transcriptional regulation of the glucocorticoid receptor (GR). Here we discuss the role of PKC/RACK1 signalling in the context of immune cells and immunosenescence also focusing on the role of cortisol and DHEA in the regulation of RACK1 expression.

Keywords

RACK1 GNB2L1 Protein kinase C (PKC) Signal transduction Transcriptional regulation Cortisol Dehydroepiandrosterone (DHEA) 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • E. Buoso
    • 1
  • Mm. Serafini
    • 1
  • M. Galasso
    • 1
  • M. Ronfani
    • 1
  • L. Poloni
    • 1
  • C. Lanni
    • 1
  • E. Corsini
    • 2
  • M. Racchi
    • 1
  1. 1.Dipartimento di Scienze del FarmacoUniversità degli Studi di PaviaPaviaItaly
  2. 2.Department of Environmental Science and PolicyUniversità degli Studi di MilanoMilanItaly

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