Hyperphosphorylation of intermediate filament proteins is involved in microcystin-LR-induced toxicity in HL7702 cells.
Toxicol Lett
; 214(2): 192-9, 2012 Oct 17.
Article
en En
| MEDLINE
| ID: mdl-22960429
Microcystin-LR (MC-LR) is commonly characterized as a hepatotoxin, which can cause disruption of keratin filaments. Keratins, however, account for only two types of intermediate filaments (IFs), and the potential involvement of other IF proteins in MC-LR-induced toxicity and the underlying mechanisms are still unclear. In this study, the human normal liver cell line HL7702 was used to investigate whether MC-LR can change the transcription, translation, and phosphorylation levels of major IF proteins and to elucidate the underlying mechanisms. The results showed that MC-LR triggered an accumulation of IFs around the nucleus and led to the formation of dense bundles. When the cells were treated with 10µM MC-LR, cell proliferation significantly decreased with an increase in apoptosis and cell cycle arrest. Moreover, the mRNA and protein levels of keratin 18, vimentin and lamin A/C were not changed; however, the phosphorylation of K8/18 and vimentin was significantly increased. Furthermore, we found MC-LR exposure caused phosphoactivation of P38, JNK and ERK1/2 in a concentration-dependent manner, and P38 and ERK1/2 were involved in MC-LR-induced hyperphosphorylation of IF proteins. Taken together, the results of this study suggest that MC-LR exerts its potential hepatotoxicity through MAPK pathway activation, which cause hyperphosphorylation of IF proteins and result in cytoskeletal architecture remodeling and cell survival/death regulation. Since IFs serve as signaling platforms and dozens of IF proteins are involved in different signaling pathways, future studies focus on different IFs may provide helpful insights into the mechanisms of MC-LR toxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Filamentos Intermedios
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Proteínas Quinasas Activadas por Mitógenos
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Microcistinas
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Proteínas de Filamentos Intermediarios
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Hígado
Límite:
Humans
Idioma:
En
Revista:
Toxicol Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos