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J Trace Elem Med Biol. 2017 May;41:119-128. doi: 10.1016/j.jtemb.2017.02.002. Epub 2017 Feb 6.

Inorganic mercury prevents the differentiation of SH-SY5Y cells: Amyloid precursor protein, microtubule associated proteins and ROS as potential targets.

Author information

1
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.
2
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.
3
Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, 07360, Mexico.
4
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.

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.

KEYWORDS:

Amyloid precursor protein; Inorganic mercury; NO; Neuronal differentiation; Neurotoxicity; ROS

PMID:
28209268
DOI:
10.1016/j.jtemb.2017.02.002
[Indexed for MEDLINE]

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