例如:"lncRNA", "apoptosis", "WRKY"

Disposition of Mianserin and Cyclizine in UGT2B10-Overexpressing Human Embryonic Kidney 293 Cells: Identification of UGT2B10 as a Novel N-Glucosidation Enzyme and Breast Cancer Resistance Protein as an N-Glucoside Transporter.

Drug Metab. Dispos.2018 Jul;46(7):970-979. Epub 2018 Apr 24
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
+ et al

[No authors listed]

Author information
  • {{index+1}} {{ organisation }}

摘要


UDP-glucuronosyltransferases (UGTs) play an important role in the metabolism and detoxification of amine-containing chemicals; however, the disposition mechanisms for amines via UGT metabolism are not fully clear. We aimed to investigate a potential role of UGT2B10 in N-glucosidation and to determine the transporters for the excretion of N-glucosides. We first established a human embryonic kidney cell line 293 (HEK293) that stably overexpressed UGT2B10. Incubation of mianserin or cyclizine with the cells generated one N-glucuronide and one N-glucoside. Chemical inhibition (using specific chemical inhibitor Ko143) and biologic inhibition [using specific short hairpin RNA of breast cancer resistance protein (BCRP)] resulted in a significant reduction in efflux of N-glucuronide. Similar results were observed when multidrug resistance-associated protein (MRP4) was inhibited. Furthermore, inhibition of BCRP led to increased intracellular N-glucoside, whereas inhibition of MRP4 caused no changes in disposition of N-glucoside. Overall, the data indicated that BCRP, not MRP4, was responsible for the excretion of N-glucosides, whereas both BCRP and MRP4 contributed to excretion of N-glucuronides. Interestingly, downregulation of N-glucuronidation led to increased N-glucosidation in the cells, supporting the glucosidation as a potential complementary pathway for conventional glucuronidation. In conclusion, UGT2B10 was for the first time identified as an N-glucosidation enzyme. Generated N-glucosides were excreted primarily by the BCRP transporter.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}

基因功能


  • {{$index+1}}.{{ gene }}

图表


原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
{{attr}}
{{ dataList.sampleTitle }}
{{ dataList.organism }} {{ dataList.expermentTitle }} {{ dataList.sampleType }} {{ dataList.libraryInstrument }} {{ showAttributeName(index,attr,dataList.attributes) }}

文献解读