IAPE1/Ref-1/I Inhibits Adipogenic Transcription Factors during Adipocyte Differentiation in 3T3-L1 Cells

• Published in: International journal of molecular sciences 2023-02, Vol.24 (4)
• Main Authors: Lee, Eun-Ok, Joo, Hee-Kyoung, Lee, Yu-Ran, Kim, Sungmin, Lee, Kwon-Ho, Lee, Sang-Do, Jeon, Byeong-Hwa
• Format: Article
• Language: English
• Subjects: DNA binding proteins; Protein binding; RNA; Type 2 diabetes
• ISSN: 1422-0067
• DOI: 10.3390/ijms24043251

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of APE1/Ref-1 is involved in inflammatory responses and regulation of DNA binding of transcription factors related to cell survival pathways. However, the effect of APE1/Ref-1 on adipogenic transcription factor regulation remains unknown. In this study, we investigated the effect of APE1/Ref-1 on the regulation of adipocyte differentiation in 3T3-L1 cells. During adipocyte differentiation, APE1/Ref-1 expression significantly decreased with the increased expression of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBP)-α and peroxisome proliferator-activated receptor (PPAR)-γ, and the adipocyte differentiation marker adipocyte protein 2 (aP2) in a time-dependent manner. However, APE1/Ref-1 overexpression inhibited C/EBP-α, PPAR-γ, and aP2 expression, which was upregulated during adipocyte differentiation. In contrast, silencing APE1/Ref-1 or redox inhibition of APE1/Ref-1 using E3330 increased the mRNA and protein levels of C/EBP-α, PPAR-γ, and aP2 during adipocyte differentiation. These results suggest that APE1/Ref-1 inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting that APE1/Ref-1 is a potential therapeutic target for regulating adipocyte differentiation.