Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D-Protein Kinase Cε-Dependent Mechanism in NeuronsReportar como inadecuado




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Background

The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A OA is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction.

Methods

In primary cortical cell cultures from newborn rats’ brains, live cell light microscopy was used to measure neurite retraction after propofol 2 µM treatment with or without OA 10 nM application. The intracellular signalling involved was tested using a protein kinase C PKC activator phorbol 12-myristate 13-acetate PMA and inhibitors of Rho-kinase HA-1077, phospholipase D PLD 5-fluoro-2-indolyl des-chlorohalopemide FIPI, PKC staurosporine, and a PKCε translocation inhibitor peptide. Changes in PKCε Ser729 phosphorylation were detected with Western blot.

Results

The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKCε translocation inhibitor peptide. OA increases via PLD and propofol decreases PKCε Ser729 phosphorylation, a crucial step in the activation of PKCε.

Conclusions

Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD-PKCε-mediated pathway, and PKCε maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge.



Autor: Karin Björnström , Dean Turina, Tobias Strid, Tommy Sundqvist, Christina Eintrei

Fuente: http://plos.srce.hr/



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