Delta opioid agonists attenuate TAT1-72-induced oxidative stress in SK-N-SH cells

David R. Wallace, Summer L. Dodson, Avindra Nath, Rosemarie M. Booze

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Previous reports have indicated that the use of δ agonists may prove to be a viable therapeutic tool as an analgesic agent without conventional opioid side effects. In addition, recent evidence suggests that δ ligands may exert neuroprotective effects under a variety of toxin insults. The aim of the present studies was to assess the ability of δ agonists (peptide: [D-Pen2,5] enkephalin (DPDPE), non-peptide: (+)-4-[(aR)-a-((2S,5R)-4- allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80)) and antagonists (naltrindole) to modify dichlorofluorescein (DCFH) fluorescence in the presence of the peroxynitrite generator, 3-morpholinylsydnoneimine chloride (SIN-1) or HIV-protein, TAT1-72 (TAT) in SK-N-SH cells. Both DPDPE (100 nM) and SNC-80 (250 nM) attenuated (30-50%) the increased oxidative stress in the presence of SIN-1. This effect was partially reversed by addition of naltrindole, suggesting involvement of δ receptors. Peroxynitrite radicals are involved in neurotoxicity associated with TAT. Incubation with TAT (10-250 nM) demonstrated a concentration-dependent increase in oxidative stress up to 200% over control values. Preincubation with δ agonists reduced 50 nM TAT-mediated oxidative stress 15-40%, which was partially reversed by naltrindole. Increasing log-concentrations of DPDPE or SNC-80 (0.01-100 μM) attenuated TAT-mediated oxidative stress up to 50% at 100 μM. In conclusion, these data demonstrate that both peptide and non-peptide delta agonists can partially attenuate intracellular oxidative stress, in part through a receptor-mediated mechanism. This suggests that delta ligands may have therapeutic usefulness in HIV patients beyond analgesia.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalNeuroToxicology
Volume27
Issue number1
DOIs
StatePublished - 1 Jan 2006

Keywords

  • Delta opioid
  • HIV
  • Neurotoxicity
  • Oxidative stress
  • Peroxynitrite
  • TAT

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