Up-regulation of PUMA caused the activation of p53 phosphorylation and acetylation, enhancing the interaction between PUMA and Bcl-X and mediating arsenic-induced apoptosis.
Toxicol Appl Pharmacol
; 434: 115800, 2022 01 01.
Article
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| MEDLINE
| ID: mdl-34798143
ABSTRACT
Arsenic is a toxic metalloid vastly dispersed all over the occupational environments, manifesting multiple adverse health issues related to apoptosis. PUMA (p53 up-regulated modulator of apoptosis) is a crucial member of the Bcl-2 protein family and plays a key role in pro-apoptosis. The purpose of this work was to determine whether inorganic arsenic (NaAsO2) and its metabolites influenced the expression of PUMA in vivo and vitro, followed by investigating the mechanisms. RNA was extracted from serum and used to determine the expression of PUMA in vivo. The urine samples performed arsenic speciation analysis. This trial tested three-dose proportions in two cell lines (A549 20, 40, 60⯵M/L; 16HBE 1.5, 3.0, 4.5⯵M/L), respectively. According to the results of qRT-PCR and western blotting, NaAsO2 caused the overexpression of PUMA, not its metabolites. Furthermore, NaAsO2 induced phosphorylation of p53 at Ser315, 376, 392, and Thr55, and acetylation of p53 at K370, 382 with a dose-response relationship, suggesting the contribution of PUMA up-regulation to p53 phosphorylation and acetylation. CCK-8, JC-1 (5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetramethylbenzimi-dazolylcarbocyanine iodide), Hoechst33342/PI and the caspase3 and PARP1 blots were utilized to reveal apoptosis responding to NaAsO2 exposure. The co-immunoprecipitation assay showed that the interaction between PUMA and Bcl-X enhanced in intensity responding to NaAsO2 exposure, disrupting the complexes of Bcl-X with other pro-survival Bcl-2-related proteins. To our knowledge, we first reported that NaAsO2 activated phosphorylation of p53 at Ser315, 376, and Thr55, as well as acetylation of p53 at K370.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Arsénico
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Proteína p53 Supresora de Tumor
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Proteínas Proto-Oncogénicas
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Apoptosis
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Proteínas Reguladoras de la Apoptosis
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Proteína bcl-X
Límite:
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China