TY - JOUR
T1 - Comparative study on methyl- and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake
AU - Zimmermann, Luciana T.
AU - Santos, Danúbia B.
AU - Naime, Aline A.
AU - Leal, Rodrigo B.
AU - Dórea, José G.
AU - Barbosa, Fernando
AU - Aschner, Michael
AU - Rocha, João Batista T.
AU - Farina, Marcelo
N1 - Funding Information:
Luciana Teixeira Zimmermann is a recipient of a post-doctoral fellowship from CAPES-PRODOC (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES – 2826/2010). The study was supported in part by funds from (i) IBN-Net/CNPq (MF, RBL and JBTR), (ii) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (MF, JBTR, FBJr, RBL and JGD), (iii) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (MF, JBTR, FBJr, RBL and JGD), (iv) INCT-CNPq-Excitotoxicity and Neuroprotection (MF and JBTR), and (v) US PHS NIH grants R01 ES07331 and ES000267 (MA).
PY - 2013/9
Y1 - 2013/9
N2 - Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p<0.0001) decreases in cellular viability when cells were treated during 30min with each mercurial following by a washing period of 24h (EC50 values of 4.83 and 5.05μM, respectively). Significant cytotoxicity (p<0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37μM). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p=0.028) and EtHg-S-Cys (p=0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system.
AB - Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p<0.0001) decreases in cellular viability when cells were treated during 30min with each mercurial following by a washing period of 24h (EC50 values of 4.83 and 5.05μM, respectively). Significant cytotoxicity (p<0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37μM). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p=0.028) and EtHg-S-Cys (p=0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system.
KW - Ethylmercury
KW - L-Type neutral amino acid carrier transport
KW - Methylmercury
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84879594818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879594818&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2013.05.015
DO - 10.1016/j.neuro.2013.05.015
M3 - Article
C2 - 23727015
AN - SCOPUS:84879594818
SN - 0161-813X
VL - 38
SP - 1
EP - 8
JO - Neurotoxicology
JF - Neurotoxicology
ER -