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Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: Correlations with amphetamine-induced neurotoxicity
- Source :
- Toxicology. 306:147-156
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- Male
Proteomics
Blotting, Western
Pharmacology
Toxicology
Pleiotrophin
Neuroprotection
Aldehyde Dehydrogenase 1 Family
Mice
Neurotrophic factors
medicine
Animals
Annexin A7
Electrophoresis, Gel, Two-Dimensional
Phosphorylation
Amphetamine
Creatine Kinase
Mice, Knockout
Midkine
biology
COP9 Signalosome Complex
Chemistry
Intracellular Signaling Peptides and Proteins
Neurotoxicity
Retinal Dehydrogenase
Aldehyde Dehydrogenase
Methamphetamine
medicine.disease
Molecular biology
Corpus Striatum
Gene Expression Regulation
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Knockout mouse
biology.protein
Cytokines
Neurotoxicity Syndromes
Carrier Proteins
Peptide Hydrolases
medicine.drug
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 306
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....b27e09dd687b7062afb260888d1f1a7c