Interleukin-1β and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent destabilization of protein and NO-dependent decrease of mRNA

Carlos E. Pedraza, María Antonia Baltrons, Michael T. Heneka, Agustina García

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21 Citations (Scopus)

Abstract

We previously showed that soluble guanylyl cyclase (sGC) is down-regulated in astroglial cells after exposure to LPS. Here, we show that this effect is not mediated by released IL-1β but that this cytokine is also able to decrease NO-dependent cGMP accumulation in a time- and concentration-dependent manner. The effect of IL-1β is receptor-mediated, mimicked by tumor necrosis factor-α and involves a decrease in sGC activity and protein. IL-1β and LPS decrease the half-life of the sGC β1 subunit by a NO-independent but transcription- and translation-dependent mechanism. Additionally, both agents induce a NO-dependent decrease of sGC subunit mRNA. Decreased sGC subunit protein and mRNA levels are also observed in adult rat brain after focal injection of IL-1β or LPS. © 2003 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)80-90
JournalJournal of Neuroimmunology
Volume144
DOIs
Publication statusPublished - 1 Jan 2003

Keywords

  • Astroglia
  • CGMP
  • Interleukin-1β
  • Lipopolysaccharide
  • Nitric oxide
  • Soluble guanylyl cyclase

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