Activation of Egr-1 expression in astrocytes by HIV-1 Tat: New insights into astrocyte-mediated Tat neurotoxicity

Yan Fan, Wei Zou, Linden A. Green, Byung Oh Kim, Johnny J. He

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system. We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300 and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the site-directed mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalJournal of Neuroimmune Pharmacology
Volume6
Issue number1
DOIs
StatePublished - Mar 2011

Keywords

  • Egr-1
  • HIV-1 Tat
  • SRE
  • astrocytes
  • p300
  • transcription activation

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