(+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia.

Abstract

BACKGROUND/PURPOSE:

Microglia have a crucial role in maintaining neuronal homeostasis in the central nervous system. Immune factors released from microglia have important roles in nociceptive signal transduction. Activation of microglia seems to be a shared mechanism in pathological pain and morphine tolerance because pharmacological attenuation of microglia activation provides satisfactory management in both situations.

METHODS:

In the present study, we investigated the effect of 1nM (+)-naloxone, which is not an opioid receptor antagonist, on morphine-induced activation of microglia EOC13.31 cells.

RESULTS:

Our results showed that 1μM morphine enhanced microglia activation and migration, decreased α-tubulin acetylation, and induced heat shock protein 90 (HSP90) fragmentation and histone deacetylase 6 (HDAC6) expression. Morphine-induced α-tubulin deacetylation and HSP90 fragmentation were HDAC6-dependent. Pretreatment with (+)-naloxone (1nM) inhibited morphine-evoked microglia activation and chemotaxis and prevented α-tubulin deacetylation and HSP90 fragmentation by inhibiting HDAC6 expression.

CONCLUSION:

Based on the findings of the present study, we suggest that (+)-naloxone inhibits morphine-induced microglia activation by regulating HDAC6-dependent α-tubulin deacetylation and HSP90 fragmentation.

• Authors: Ru-Yin Tsai, Yu-Che Cheng, Chih-Shung Wong
• Journal: Journal of the Formosan Medical Association = Taiwan yi zhi (J Formos Med Assoc) Vol. 114 Issue 5 Pg. 446-55 (May 2015) ISSN: 0929-6646 [Print] Singapore
• PMID: 25649471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• HSP90 Heat-Shock Proteins
• Hspca protein, mouse
• Narcotic Antagonists
• Tubulin
• Naloxone
• Morphine
• Hdac6 protein, mouse
• Histone Deacetylase 6
• Histone Deacetylases

Topics

• Animals
• Cell Line
• Chemotaxis (drug effects)
• HSP90 Heat-Shock Proteins (metabolism)
• Histone Deacetylase 6
• Histone Deacetylases (metabolism)
• Mice
• Microglia (metabolism)
• Morphine (pharmacology)
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Signal Transduction
• Tubulin (metabolism)