Selenium ameliorates cadmium-induced mouse leydig TM3 cell apoptosis via inhibiting the ROS/JNK /c-jun signaling pathway.
Ecotoxicol Environ Saf
; 192: 110266, 2020 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-32058163
ABSTRACT
Despite the well-known acknowledgement of both the toxicity of cadmium (Cd) and the ameliorative effect of selenium (Se), the mechanism of the protective effect of selenium on cadmium-induced Mouse Leydig (TM3) cell apoptosis remains unknown. In this study, we hypothesized that the reactive oxygen species (ROS)-mediated c-jun N-terminal kinase (JNK) signaling pathway is involved in anti-apoptosis of selenium against cadmium in TM3 cells. We found that exposure to cadmium caused evident cytotoxicity, in which cell viability was inhibited, followed by inducement of apoptosis. Moreover, the level of ROS generation was elevated, leading to the phosphorylation of JNK. In addition, following cadmium exposure, the nuclear transcription factor c-jun was significantly activated, which led to increased expression of downstream gene c-jun, resulting in downstream activation of the apoptosis-related protein Caspase3 and upregulation of Cleaved-PARP, as well as inhibition of the anti-apoptosis protein Bcl-2. However, pretreatment with selenium remarkably suppressed cadmium-induced TM3 cell apoptosis. Furthermore, the level of ROS declined, and the JNK signaling pathway was blocked. Following this, the gene expression of c-jun decreased while Bcl-2 increased, which was consistent with the effects on proteins, that Caspase3 activity and Cleaved-PARP were inhibited while Bcl-2 level was restored. In order to explain the relationship between molecules of the signaling pathway, N-acetyl-L-cysteine (NAC), the ROS inhibitor, and JNK1/2 siRNA were administered, which further indicated the mediatory role of the ROS/JNK/c-jun signaling pathway in regulating anti-apoptosis of selenium against cadmium-induced TM3 cell apoptosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Selênio
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Cádmio
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Espécies Reativas de Oxigênio
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Apoptose
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Proteínas Quinases JNK Ativadas por Mitógeno
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Células Intersticiais do Testículo
Limite:
Animals
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Ano de publicação:
2020
Tipo de documento:
Article