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Orexin A Inhibits P...
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, Karin (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Anestesi- och intensivvårdskliniken US
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- Turina, Dean (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet
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- Strid, Tobias (author)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Hälsouniversitetet
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- Sundqvist, Tommy (author)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet
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- Eintrei, Christina (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Anestesi- och intensivvårdskliniken US
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(creator_code:org_t)
- 2014-05-14
- 2014
- English.
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:5, s. e0097129-
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Abstract
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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