title: Paraoxon and Pyridostigmine Interfere with Neural Stem Cell Differentiation.
abstract: Acetylcholinesterase (AChE) inhibition has been described as the main mechanism of organophosphate (OP)-evoked toxicity. OPs represent a human health threat, because chronic exposure to low doses can damage the developing brain, and acute exposure can produce long-lasting damage to adult brains, despite post-exposure medical countermeasures. Although the main mechanism of OP toxicity is AChE inhibition, several lines of evidence suggest that OPs also act by other mechanisms. We hypothesized that rat neural progenitor cells extracted on embryonic day 14.5 would be affected by constant inhibition of AChE from chronic exposure to OP or pyridostigmine (a reversible AChE blocker) during differentiation. In this work, the OP paraoxon decreased cell viability in concentrations >50 μM, as measured with the MTT assay; however, this effect was not dose-dependent. Reduced viability could not be attributed to blockade of AChE activity, since treatment with 200 µM pyridostigmine did not affect cell viability, even after 6 days. Although changes in protein expression patterns were noted in both treatments, the distribution of differentiated phenotypes, such as the percentages of neurons and glial cells, was not altered, as determined by flow cytometry. Since paraoxon and pyridostigmine each decreased neurite outgrowth (but did not prevent differentiation), we infer that developmental patterns may have been affected.
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Ave. Laurel #100, Santa Juanita, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: Verónica O
authors.initials: VO
authors.lastname: Berríos
authors.affiliation: Department of Microbiology and Immunology, Biomedical Proteomics Facility, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: Nawal M
authors.initials: NM
authors.lastname: Boukli
authors.affiliation: Department of Microbiology and Immunology, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: Jose W
authors.initials: JW
authors.lastname: Rodriguez
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, Brazil.
authors.forename: Priscilla D
authors.initials: PD
authors.lastname: Negraes
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, Brazil.
authors.forename: Telma T
authors.initials: TT
authors.lastname: Schwindt
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, Brazil.
authors.forename: Cleber A
authors.initials: CA
authors.lastname: Trujillo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, Brazil.
authors.forename: Sophia L B
authors.initials: SL
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Ave. Laurel #100, Santa Juanita, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Cubano
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Ave. Laurel #100, Santa Juanita, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Ferchmin
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Ave. Laurel #100, Santa Juanita, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
authors.forename: Vesna A
authors.initials: VA
authors.lastname: Eterović
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, Brazil.
authors.forename: Henning
authors.initials: H
authors.lastname: Ulrich
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Ave. Laurel #100, Santa Juanita, P.O. Box 60327, Bayamón, PR, 00960-6032, USA. baccin31@gmail.com.
authors.forename: Antonio H
authors.initials: AH
authors.lastname: Martins
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010261:Paraoxon; D011729:Pyridostigmine Bromide / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide; D010261:Paraoxon
keywords: Differentiation; Neural progenitor cells; Organophosphates; Paraoxon; Proteomics