Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: Correlations with amphetamine-induced neurotoxicity

Gramage, Esther; Herradón, Gonzalo; Martín, Yasmina B.; Vicente-Rodríguez, Marta; Rojo, Loreto; Gnekow, Heike; Barbero, Aurora; Pérez-Garcı́a, Carmen

doi:10.1016/j.tox.2013.02.013

Cited by 20 publications

(51 citation statements)

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“…The phosphoprotein yield ranged from 8.0 to 12.0% of the total protein content which is in agreement with previous studies. 15,30 Proteins were then separated by 2D-PAGE. The gels (n = 5 per group) obtained from the 6 experimental groups were analyzed simultaneously and matched in the same set.…”

Section: ■ Resultsmentioning

confidence: 99%

Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin

Vicente-Rodríguez

Herradón

Ferrer-Alcón

et al. 2015

Chem. Res. Toxicol.

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The neurotrophic factor pleiotrophin (PTN) is upregulated in different brain areas after the administration of different drugs of abuse, including psychostimulants. PTN has been shown to prevent cocaine-induced cytotoxicity in NG108-15 and PC12 cells. We previously demonstrated that specific phosphoproteins related to neurodegeneration processes are differentially regulated in the mouse striatum by a single cocaine (15 mg/kg) administration depending on the endogenous expression of PTN. Since neurodegenerative processes are usually observed in patients exposed to toxicants for longer duration, we have now performed a striatal proteomic study using samples enriched in phosphorylated proteins from PTN knockout (PTN-/-) mice, from mice with transgenic PTN overexpression (PTN-Tg) in the brain, and from wild type (WT) mice after a chronic treatment with cocaine (15 mg/kg/day for 7 days). We have successfully identified 23 proteins significantly affected by chronic cocaine exposure, genotype, or both. Most of these proteins, including peroxiredoxin-6 (PRDX6), triosephosphate isomerase (TPI1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), and annexins A5 (ANXA5) and A7 (ANXA7), may be of significant importance because they were previously identified in proteomic studies in animals treated with psychostimulants and/or because they are related to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. The data support a protective role of PTN against chronic cocaine-induced neural alterations.

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Section: ■ Resultsmentioning

confidence: 99%

Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin

Vicente-Rodríguez

Herradón

Ferrer-Alcón

et al. 2015

Chem. Res. Toxicol.

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“…These data suggest that both cytokines have neuroprotective roles against drug‐induced neurotoxicity and this hypothesis is supported by results from in vitro studies (Gramage et al ., 2008; 2010b). These different responses to amphetamine treatment in PTN‐/‐, MK‐/‐ and WT+/+ mice led us to use these animal models to identify druggable downstream targets in the PTN/MK signalling pathways that could modulate the amphetamine‐induced neurotoxic effects (Gramage et al ., 2013a). In proteomic studies, we identified 13 differentially expressed phosphoproteins that are judged to be relevant in the neuroprotective roles of PTN and MK against amphetamine‐induced neurotoxicity.…”

Section: Roles Of Mk and Ptn In Addiction And Neurodegenerationmentioning

confidence: 99%

“…Table summarizes the cellular function of these proteins and existing evidence supporting their possible roles in neurodegenerative diseases. Since the phosphorylation pattern of these proteins was found to be differentially regulated by amphetamine treatment and the presence/absence of endogenous MK and PTN (Gramage et al ., 2013a), the data not only confirm the connection between the molecular mechanisms of amphetamine‐induced neurotoxicity and those involved in neurodegenerative processes but suggest these four proteins could be new pharmacological targets involved in the neuroprotective effects of MK and PTN. Interestingly, some of these proteins, such as ALDH1A1, are already in screening panels for drug discovery.…”

Section: Activation Of Mk/ptn Signalling Pathways: a Novel Therapeutimentioning

confidence: 99%

Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives

Herradón

Pérez-Garcı́a

2014

British J Pharmacology

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Midkine (MK) and pleiotrophin (PTN) are two neurotrophic factors that are highly up-regulated in different brain regions after the administration of various drugs of abuse and in degenerative areas of the brain. A deficiency in both MK and PTN has been suggested to be an important genetic factor, which confers vulnerability to the development of the neurodegenerative disorders associated with drugs of abuse in humans. In this review, evidence demonstrating that MK and PTN limit the rewarding effects of drugs of abuse and, potentially, prevent drug relapse is compiled. There is also convincing evidence that MK and PTN have neuroprotective effects against the neurotoxicity and development of neurodegenerative disorders induced by drugs of abuse. Exogenous administration of MK and/or PTN into the CNS by means of non-invasive methods is proposed as a novel therapeutic strategy for addictive and neurodegenerative diseases. Identification of new molecular targets downstream of the MK and PTN signalling pathways or pharmacological modulation of those already known may also provide a more traditional, but probably effective, therapeutic strategy for treating addictive and neurodegenerative disorders. LINKED ARTICLESThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2014.171.issue-4 Abbreviations ALDH1A1, aldehyde dehydrogenase family 1 member A1; ALK, anaplastic lymphoma kinase; ANXA7, annexin; BBB, blood brain barrier; CKMT1, creatine kinase U-type; COPS5, COP9 signalosome subunit 5; CPP, conditioned place preference; KA, kainic acid; MK, midkine; NGF, nerve growth factor; PD, Parkinson's disease; PTK, protein tyrosine kinase; PTN, pleiotrophin; PTP, protein tyrosine phosphatase; PTPRZ, protein tyrosine phosphatase type Z IntroductionThe neurotoxic effects of drugs of abuse underlie not only drug-seeking behaviours but also the neurodegeneration processes associated with chronic drug consumption . For example, chronic alcohol consumption is associated with an increase in the incidence of a variety of diseases, including CNS degeneration (Collins and Neafsey, 2012). These addictive and neurotoxic effects of psychostimulants and other drugs of abuse have been associated with enhanced damage of dopaminergic neurons in the nigrostriatal pathway (Ferrucci et al., 2008;Valverde and Rodríguez-Árias, 2013). Drugs of abuse promote the intracellular accumulation of dopamine (Kalivas and O'Brien, 2008), which could elicit neuronal death by blocking mitochondrial complex 1, as occurs, for example, with Parkinsonian agents (Fahn and Sulzer, 2004). In addition, cocaine has been shown to cause significant increases in α-synuclein levels in dopaminergic neurons (Mash et al., 2003). Interestingly, α-synuclein is known to be the main component of Lewy bodies in patients with Parkinson's disease (PD) (Spillantini et al., 1997). Furthermore, it was recently found that BJP British Journal of Pharmacology DOI:10.1111/bph.12312 www.brjpharmacol.org Briti...

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“…Two recent studies (Vicente-Rodriguez et al, 2013;Gramage et al, 2013) using pleiotrophin-knockout and midkine-knockout mice to investigate oxidative stress pathways finds several differentially expressed phosphoproteins in the striatum induced by cocaine and amphetamine. These changes were first reported to be associated with the oxidative stress response.…”

Section: Proteomic Studies On Drug Addictionmentioning

confidence: 99%

“…Some proteins, such as Hsp70, peroxiredoxin-6, αand β-synuclein, have been reported in several studies. They correlate with exposure to different drugs, including methamphetamine, morphine, cocaine, alcohol and marijuana (Wang et al, 2011;Bu et al, 2012;Vicente-Rodriguez et al, 2013). These proteins are commonly involved in protein modification/degradation pathway, or oxidative stress response or synaptic function,…”

Section: Proteomic Studies On Drug Addictionmentioning

confidence: 99%

The potential biomarkers of drug addiction: proteomic and metabolomics challenges

Lv¹,

Wu²,

Zhao³

et al. 2016

Biomarkers

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Drug addiction places a significant burden on society and individuals. Proteomics and metabolomics approaches pave the road for searching potential biomarkers to assist the diagnosis and treatment. This review summarized putative drug addiction-related biomarkers in proteomics and metabolomics studies and discussed challenges and prospects in future studies. Alterations of several hundred proteins and metabolites were reported when exposure to abused drug, which enriched in energy metabolism, oxidative stress response, protein modification and degradation, synaptic function and neurotrasmission, etc. Hsp70, peroxiredoxin-6 and α- and β-synuclein, as well as n-methylserotonin and purine metabolites, were promising as potential biomarker for drug addiction.

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Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: Correlations with amphetamine-induced neurotoxicity

Cited by 20 publications

References 59 publications

Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin

Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin

Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives

The potential biomarkers of drug addiction: proteomic and metabolomics challenges

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