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The essential role of GSTP1 I105V polymorphism in the prediction of CDNB metabolism and toxicity: In silico and in vitro insights

Lin, Hao ; Wu, Han ; Li, Hengda ; Song, Aoqi ; Yin, Wu

Toxicology in vitro, 2023-08, Vol.90, p.105601-105601, Article 105601 [Periódico revisado por pares]

England: Elsevier Ltd

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  • Título:
    The essential role of GSTP1 I105V polymorphism in the prediction of CDNB metabolism and toxicity: In silico and in vitro insights
  • Autor: Lin, Hao ; Wu, Han ; Li, Hengda ; Song, Aoqi ; Yin, Wu
  • Assuntos: CDNB ; Docking ; Genotype ; Glutathione S-Transferase pi - genetics ; Glutathione Transferase - genetics ; Glutathione Transferase - metabolism ; GSTP1 ; Humans ; I105V polymorphism ; Molecular Docking Simulation ; Molecular dynamics ; Polymorphism, Single Nucleotide
  • É parte de: Toxicology in vitro, 2023-08, Vol.90, p.105601-105601, Article 105601
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Humans are continuously exposed to toxic chemicals such as nitro-chlorobenzene (CDNB) through occupation, water, and even the air we breathe. Due to the severe toxicity caused by the high electrophilicity of CDNB, occupational and environmental exposure to CDNB can produce toxic effects that ultimately lead to cell damage. CDNB can be eliminated from organisms by binding to GSH, the catalytic product of glutathione S-transferase P1 (GSTP1). Therefore, GSTP1 plays an important role in the detoxification of CDNB. However, subtle variations in GSTP1 can result in single nucleotide polymorphisms (SNPs). Indeed, the correlation between the clinical outcome of the disease and certain genotypes of GSTP1 has been extensively studied, however, their impact on the metabolic detoxification of toxicants such as CDNB remains to be elucidated. Among the various SNPs of GSTP1, I105V has a significant effect on the catalytic activity of GSTP1. In this paper, a GSTP1 I105V polymorphism model was successfully established, and its effect on CDNB metabolism and toxicity was studied by computer analysis including molecular docking and molecular dynamics simulation. The result demonstrated that the binding capacity of CDNB decreases with the I105V mutation of GSTP1(p < 0.001), indicating the changes in its detoxification efficacy in CDNB-induced cell damage. Organisms expressing GSTP1 V105 are more susceptible to cell damage caused by CDNB than individuals expressing GSTP1 I105 (p < 0.001). In sum, the data in this study provide prospective insights into the mechanism and capacity of CDNB detoxification in the GSTP1 allele, extending the CDNB-mediated toxicological profile. In addition, the heterogeneity of the GSTP1 allele should be included in toxicological studies of individuals exposed to CDNB. •Single nucleotide polymorphisms of GSTP1 lead to CDNB metabolism and toxicity changes.•GSTP1 I105 exhibited preferable catalytic activities than GSTP1 V105 in the conjugation reaction of CDNB.•Organisms expressing GSTP1 V105 are more susceptible to cell damage caused by CDNB than individuals expressing GSTP1 I105.•CDNB might induce more ROS generation leading to damage when the organism expressed GSTP1 V105.
  • Editor: England: Elsevier Ltd
  • Idioma: Inglês
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