title: Inorganic mercury prevents the differentiation of SH-SY5Y cells: Amyloid precursor protein, microtubule associated proteins and ROS as potential targets.
abstract: Exposure to mercury (Hg) occurs through different pathways and forms including methylmecury (MeHg) from seafood and rice, ethylmercury (EtHg), and elemental Hg (Hg0) from dental amalgams and artisanal gold mining. Once in the brain all these forms are transformed to inorganic Hg (I-Hg), where it bioaccumulates and remains for long periods. Hg is a well-known neurotoxicant, with its most damaging effects reported during brain development, when cellular key events, such as cell differentiation take place. A considerable number of studies report an impairment of neuronal differentiation due to MeHg exposure, however the effects of I-Hg, an important form of Hg found in brain, have received less attention. In this study, we decided to examine the effects of I-Hg exposure (5, 10 and 20μM) on the differentiation of SH-SY5Y cells induced by retinoic acid (RA, 10μM). We observed extension of neuritic processes and increased expression of neuronal markers (MAP2, tubulin-βIII, and Tau) after RA stimulation, all these effects were decreased by the co-exposure to I-Hg. Interestingly, I-Hg increased the levels of reactive oxygen species (ROS) and nitric oxide (NO) accompanied with increased levels of inducible nitric oxide synthase (iNOS) and, dimethylarginine dimethylaminohydrolase 1 (DDHA1). Remarkably I-Hg decreased levels of nitric oxide synthase neuronal (nNOS). Moreover I-Hg reduced the levels of tyrosine hydroxylase (TH) and amyloid precursor protein (APP) a protein recently involved in neuronal differentiation. These data suggest that the exposure to I-Hg impairs cell differentiation, and point to new potential targets of Hg toxicity such as APP and NO signaling.
authors.affiliation: Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico; Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Campeche, Campeche 4039, Mexico.
authors.forename: Miguel Chin
authors.initials: MC
authors.lastname: Chan
authors.affiliation: Departmento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico; Facultad de Ciencias de la Salud, Universidad Anáhuac Norte, 52786, Huixquilucan, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bautista
authors.affiliation: Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico.
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarado-Cruz
authors.affiliation: Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico.
authors.forename: Betzabet
authors.initials: B
authors.lastname: Quintanilla-Vega
authors.affiliation: Departmento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico. Electronic address: jsegovia@fisio.cinvestav.mx.
authors.forename: José
authors.initials: J
authors.lastname: Segovia
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008628:Mercury / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D014212:Tretinoin; D008628:Mercury
keywords: Amyloid precursor protein; Inorganic mercury; NO; Neuronal differentiation; Neurotoxicity; ROS