Pleiotrophin prevents cocaine-induced toxicity in vitro

European Journal of Pharmacology
Esther GramageGonzalo Herradon

Abstract

Pleiotrophin is a cytokine involved in differentiation, survival and repair processes in the central nervous system. Pleiotrophin is upregulated in the brain after administration of different drugs of abuse, thus suggesting a protective role of this cytokine on drug-induced toxicity. We have tested this hypothesis in vitro using NG108-15 cells, a line widely used for neurotoxicity studies. It was found that pleiotrophin (3 and 6 microM) significantly prevents cocaine (5 mM)-induced cytotoxicity as measured by the neutral red test. Similar results were obtained in PC12 cells, which were found to endogenously express both pleiotrophin and its main target, receptor protein tyrosine phosphatase (RPTP) beta/zeta. Blockade of pleiotrophin signaling using anti-pleiotrophin antibodies (2 microg/ml) did not potentiate cocaine-induced toxicity; interestingly, incubation of PC12 cells only with anti-pleiotrophin antibodies significantly reduced cellular viability, thus suggesting an important role of endogenous pleiotrophin signaling in cell survival. The data suggest that pleiotrophin overexpression in response to drugs of abuse may be relevant to prevent drug-induced toxicity.

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Citations

Jun 9, 2011·Molecular Neurodegeneration·Irene Re TaraviniOscar S Gershanik
Oct 26, 2010·European Journal of Pharmacology·Ran NumaRami Yaka
Jun 6, 2009·European Journal of Pharmacology·Jenny SchneebergKlaus G Reymann
Sep 20, 2011·Cell Biochemistry and Function·Hitomi AsaiSeiji Miyata
Jul 31, 2014·Journal of Neurochemistry·Marta Vicente-RodríguezGonzalo Herradón
Aug 9, 2011·Molecular and Cellular Neurosciences·Suvarna Dash-WaghPetra Wahle
Sep 20, 2016·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Marta Vicente-RodríguezGonzalo Herradón
Feb 11, 2018·Scientific Reports·Ramesh B BadisaCarl B Goodman
Sep 26, 2015·Pharmacological Reviews·Esa R KorpiGavin S Dawe
Apr 21, 2018·Neural Plasticity·Dawn E MuskiewiczF Scott Hall
Jun 6, 2015·Chemical Research in Toxicology·Marta Vicente-RodríguezCarmen Pérez-García

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