Inorganic mercury prevents the differentiation of SH-SY5Y cells: Amyloid precursor protein, microtubule associated proteins and ROS as potential targets.
J Trace Elem Med Biol
; 41: 119-128, 2017 May.
Article
in En
| MEDLINE
| ID: mdl-28209268
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-ßIII, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Amyloid beta-Protein Precursor
/
Reactive Oxygen Species
/
Mercury
/
Microtubule-Associated Proteins
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Trace Elem Med Biol
Journal subject:
METABOLISMO
/
SAUDE AMBIENTAL
Year:
2017
Document type:
Article
Affiliation country:
Mexico
Publication country:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY