Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase C-epsilon-Dependent Mechanism in Neurons

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Björnström-Karlsson, KarinÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Anestesi- och intensivvårdskliniken US (author)

Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase C-epsilon-Dependent Mechanism in Neurons

Article/chapterEnglish2014

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2014-05-14
Public Library of Science,2014
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:liu-108807
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-108807URI
https://doi.org/10.1371/journal.pone.0097129DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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 mu M) 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 PKC epsilon translocation inhibitor peptide. Changes in PKC epsilon Ser(729) 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 PKC epsilon translocation inhibitor peptide. OA increases via PLD and propofol decreases PKC epsilon Ser(729) phosphorylation, a crucial step in the activation of PKC epsilon. 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/PKC epsilon-mediated pathway, and PKC epsilon maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Anestesi och intensivvård hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Anesthesiology and Intensive Care hsv//eng
MEDICINE
MEDICIN

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Turina, DeanLinköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet(Swepub:liu)deatu08 (author)
Strid, TobiasLinköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Hälsouniversitetet(Swepub:liu)tobst76 (author)
Sundqvist, TommyLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet(Swepub:liu)tomsu30 (author)
Eintrei, ChristinaÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Anestesi- och intensivvårdskliniken US(Swepub:liu)chrei93 (author)
Linköpings universitetAvdelningen för läkemedelsforskning (creator_code:org_t)

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In:PLOS ONE: Public Library of Science9:5, s. e0097129-1932-6203

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