Delta opioid agonists attenuate TAT(1-72)-induced oxidative stress in SK-N-SH cells

作者：Wallace DR^*; Dodson SL; Nath A; Booze RM

来源：NeuroToxicology, 2006, 27(1): 101-107.

DOI：10.1016/j.neuro.2005.07.008

• TAT
• delta opioid
• oxidative stress
• peroxynitrite
• HIV
• neurotoxicity

Previous reports have indicated that the use of delta agonists may prove to be a viable therapeutic tool as an analgesic agent without conventional opioid side effects. In addition, recent evidence suggests that delta ligands may exert neuroprotective effects under a variety of toxin insults. The aim of the present studies was to assess the ability of delta agonists (peptide: [D-Pen(2.5)] 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, TAT(1-72) (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 8 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 delta 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 mu M) attenuated TAT-mediated oxidative stress up to 50% at 100 mu M. 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.

• 出版日期2006-1