HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in intracellular Ca2+ concentration via activation of Src kinase and nitric oxide signaling pathways.

ABSTRACT: HIV-associated neurocognitive disorders afflict about half of HIV-infected patients. HIV-infected cells shed viral proteins, such as the transactivator of transcription (Tat), which can cause neurotoxicity by over activation of NMDA receptors. Here, we show that Tat causes a time-dependent, biphasic change in NMDA-evoked increases in intracellular Ca(2+) concentration ([Ca(2+)]i). NMDA-evoked responses were potentiated following 2-h exposure to Tat (50 ng/mL). Tat-induced potentiation of NMDA-evoked increases in [Ca(2+)]i peaked by 8 h and then adapted by gradually reversing to baseline by 24 h and eventually dropping below control by 48 h. Tat-induced potentiation of NMDA-evoked responses was blocked by inhibition of lipoprotein receptor-related protein (LRP) or Src tyrosine kinase. Poten

SUBMITTER: Krogh KA 

PROVIDER: S-EPMC4141023 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature