(+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia.
J Formos Med Assoc
; 114(5): 446-55, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25649471
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quimiotaxia
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Microglia
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Proteínas de Choque Térmico HSP90
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Histona Desacetilases
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Morfina
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Naloxona
Limite:
Animals
Idioma:
En
Revista:
J Formos Med Assoc
Assunto da revista:
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Taiwan