Thioredoxin‐interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β‐cell dysfunction and exert therapeutic effects i...
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https://www.riss.kr/link?id=O112668161
2021년
-
1747-0277
1747-0285
SCI;SCIE;SCOPUS
학술저널
1089-1099 [※수록면이 p5 이하이면, Review, Columns, Editor's Note, Abstract 등일 경우가 있습니다.]
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
Thioredoxin‐interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β‐cell dysfunction and exert therapeutic effects i...
Thioredoxin‐interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β‐cell dysfunction and exert therapeutic effects in diabetic mice via repression of TXNIP signaling pathway. The impact of W2476 on TXNIP transcription was thus investigated using the chromatin immunoprecipitation method. It was found that W2476 promotes competitive binding of forkhead box O1 transcription factor (FOXO1) to the carbohydrate response element (ChoRE) sequence associated with ChoRE‐binding protein (ChREBP)/Mlx interacting protein‐like(Mlx) complexes. This interaction hinders the attachment of histone acetyltransferase p300 and reduces histone H4 acetylation on the TXNIP promoter, leading to decreasing TXNIP transcription.
The small molecule compound (W2476) promotes competitive binding of forkhead box O1 transcription factor (FOXO1) to the carbohydrate response element (ChoRE) sequence associated with ChoRE‐binding protein (ChREBP)/Mlx interacting protein‐like (Mlx) complexes. This interaction prevents the attachment of histone acetyltransferase p300 and reduces histone H4 acetylation on the TXNIP promoter, leading to decreasing TXNIP transcription.