title: Recovery of brain biomarkers following peroxisome proliferator-activated receptor agonist neuroprotective treatment before ischemic stroke.
abstract: BACKGROUND
  Lipid lowering agent such as agonists of peroxisome proliferator-activated receptors (PPAR) are suggested as neuroprotective agents and may protect from the sequelae of brain ischemic stroke. Although the demonstration is not clearly established in human, the underlying molecular mechanism may be of interest for future therapeutic purposes. To this end, we have used our well established rodent model of ischemia-reperfusion pre-treated or not with fenofibrate or atorvastatin and performed a differential proteomics analyses of the brain and analysed the protein markers which levels returned to "normal" following pre-treatments with PPARα agonists.
  
  
  RESULTS
  In order to identify potential therapeutic targets positively modulated by pre-treatment with the PPARα agonists, two-dimensional gel electrophoresis proteome profiles between control, ischemia-reperfusion and pre-treated or not, were compared. The polypeptide which expression was altered following ischemia - reperfusion but whose levels remain unchanged after pre-treatment were characterized by mass spectrometry and further investigated by Western-blotting and immunohistochemistry. A series of 28 polypeptides were characterized among which the protein disulfide isomerase reduction - a protein instrumental to the unfolded protein response system - was shown to be reduced following PPARα agonists treatment while it was strongly increased in ischemia-reperfusion.
  
  
  CONCLUSIONS
  Pre-treatment with PPARα agonist or atorvastatin show potential neuroprotective effects by inhibiting the PDI overexpression in conjunction with the preservation of other neuronal markers, several of which are associated with the regulation of protein homeostasis, signal transduction and maintenance of synaptic plasticity. This proteomic study therefore suggests that neuroprotective effect of PPARα agonists supposes the preservation of the expression of several proteins essential for the maintenance of protein homeostasis not necessarily directly linked to PPARα known-regulated targets.
authors.affiliation: Clinical Investigation center, IMPRT, University of Lille II, Cardiologic Hospital, Lille, France ; Inserm UMR 837, JPARC, Place de Verdun, Lille 59045, France ; PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France ; EA1046 - Department de Pharmacology - University of Lille 2, University Hospital Centre Place de Verdun, Lille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gelé
authors.affiliation: Inserm UMR 837, JPARC, Place de Verdun, Lille 59045, France ; PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vingtdeux
authors.affiliation: EA1046 - Department de Pharmacology - University of Lille 2, University Hospital Centre Place de Verdun, Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Potey
authors.affiliation: PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France ; UMR 8161 CNRS, Biomolecules and Micro-nanotechnologies laboratory - University of Lille 2 - University of Lille 1 - Pasteur Institute of Lille, Lille, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Drobecq
authors.affiliation: Inserm UMR 837, JPARC, Place de Verdun, Lille 59045, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Ghestem
authors.affiliation: PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France ; UMR 8161 CNRS, Biomolecules and Micro-nanotechnologies laboratory - University of Lille 2 - University of Lille 1 - Pasteur Institute of Lille, Lille, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
authors.affiliation: Inserm UMR 837, JPARC, Place de Verdun, Lille 59045, France ; PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: Inserm UMR 837, JPARC, Place de Verdun, Lille 59045, France ; PRES University Lille Nord de France, University of Lille II, Jean-Pierre Aubert Research Center, Institute of Predictive Medicine and Therapeutic Research, Lille IFR114, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.affiliation: EA1046 - Department de Pharmacology - University of Lille 2, University Hospital Centre Place de Verdun, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
keywords: Fibrate; Neuroprotection; Proteomics; Statin; Stroke