Inorganic arsenic promotes apoptosis of human immortal keratinocytes through the TGF-ß1/ERK signaling pathway.
Environ Toxicol
; 37(6): 1321-1331, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35142421
ABSTRACT
Chronic exposure to high-dose inorganic arsenic through groundwater, air, or food remains a major environmental public health issue worldwide. Apoptosis, a method of cell death, has recently become a hot topic of research in biology and medicine. Previous studies have demonstrated that extracellular signal-regulated kinase (ERK) is related to arsenic-induced apoptosis. However, the reports are contradictory, and the knowledge of the above-mentioned mechanisms and their mutual regulation remains limited. In this study, the associations between the TGF-ß1/ERK signaling pathway and arsenic-induced cell apoptosis were confirmed using the HaCaT cell model. The relative expressions of the indicators of the TGF-ß1/ERK signaling pathway, apoptosis-related genes (cytochrome C, caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9, and Bax), the mitochondrial membrane potential, and the total apoptosis rate were significantly increased (P < .05), while the expression of the antiapoptosis gene Bcl-2 was significantly decreased (P < .05) in cells of the group exposed to arsenic. Moreover, the results demonstrated that the ERK inhibitor (PD98059) and TGF-ß1 inhibitor (LY364947) could inhibit the activation of the ERK signaling pathway, thereby reducing the mitochondrial membrane potential, the total apoptosis rate, and the expression of pro-apoptosis-related genes in the cells, while the expression of the antiapoptosis gene Bcl-2 was significantly increased (P < .05). By contrast, the recombinant human TGF-ß1 could promote apoptosis of the HaCaT cells by increasing the activation of the ERK signaling pathway (P < .05). These results indicate that inorganic arsenic promotes the apoptosis of human immortal keratinocytes through the TGF-ß1/ERK signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arsênio
/
MAP Quinases Reguladas por Sinal Extracelular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Environ Toxicol
Assunto da revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China