Creatine protects against mitochondrial dysfunction associated with HIV-1 tat-induced neuronal injury

Patrick R. Stevens, Jeremy W. Gawryluk, Liang Hui, Xuesong Chen, Jonathan D. Geiger

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.

Original languageEnglish (US)
Pages (from-to)378-387
Number of pages10
JournalCurrent HIV research
Volume12
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Creatine
  • HIV-1 Tat
  • HIV-1 associated neurocognitive disorders
  • Mitochondria dysfunction
  • Neuroprotection

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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