title: Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: correlations with amphetamine-induced neurotoxicity.
abstract: The neurotrophic factors pleiotrophin (PTN) and midkine (MK) have been shown to modulate amphetamine-induced neurotoxicity. Accordingly, PTN-/- and MK-/- mice show an increased vulnerability to amphetamine-induced neurotoxic effects. In an effort to uncover new pharmacological targets to prevent amphetamine neurotoxic effects, we have now used a proteomic approach to study protein phosphorylation, in which we combined phosphoprotein enrichment, by immobilized metal affinity chromatography (IMAC), with two-dimensional gel electrophoresis and mass spectrometry, in order to identify the phosphoproteins regulated in the striatum of PTN-/-, MK-/- and wild type (WT) mice treated with amphetamine. We identified 13 differentially expressed phosphoproteins that are judged to be relevant in the neuroprotective roles of PTN and MK against amphetamine-induced neurotoxicity. It is very interesting to note that 4 of these phosphoproteins, annexin A7 (ANXA7), COP9 signalosome subunit 5 (COPS5), aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and creatine kinase U-type (CKMT1), are known to be involved in Parkinson's disease, a result of significant importance since PTN and MK have been also demonstrated to limit Parkinson's disease (PD) progress and have been suggested to be among the important genetic factors possibly preventing the development of PD in methamphetamine abusers. The data identify phosphoproteins differentially regulated by amphetamine treatment and/or the presence of endogenous PTN/MK which may be relevant mediators of PTN/MK neuroprotective effects against amphetamine-induced neurotoxicity. The data support further studies to validate the phosphoproteins here identified as possible new pharmacological targets to prevent amphetamine neurotoxic effects.
authors: Pharmacology Lab, Department of Pharmaceutical and Food Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors: Esther
authors: E
authors: Gramage
authors: Gonzalo
authors: G
authors: Herradón
authors: Yasmina B
authors: YB
authors: Martín
authors: Marta
authors: M
authors: Vicente-Rodríguez
authors: Loreto
authors: L
authors: Rojo
authors: Heike
authors: H
authors: Gnekow
authors: Aurora
authors: A
authors: Barbero
authors: Carmen
authors: C
authors: Pérez-García
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D017310:Annexin A7 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000078792:Midkine; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D040901:Proteomics; D050697:Retinal Dehydrogenase; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017310:Annexin A7; C480504:Anxa7 protein, mouse; D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C066845:pleiotrophin; D000078792:Midkine; D000661:Amphetamine; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D003402:Creatine Kinase; D010447:Peptide Hydrolases; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex