<i>APE1/Ref-1</i> Inhibits Adipogenic Transcription Factors during Adipocyte Differentiation in 3T3-L1 Cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (<i>APE1/Ref-1</i>) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of <i>APE1/Ref-1</i> is involved in inflammatory responses and regulation of DNA binding of transcription facto...

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Main Authors: Eun-Ok Lee, Hee-Kyoung Joo, Yu-Ran Lee, Sungmin Kim, Kwon-Ho Lee, Sang-Do Lee, Byeong-Hwa Jeon
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/4/3251
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Summary:Apurinic/apyrimidinic endonuclease 1/redox factor-1 (<i>APE1/Ref-1</i>) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of <i>APE1/Ref-1</i> is involved in inflammatory responses and regulation of DNA binding of transcription factors related to cell survival pathways. However, the effect of <i>APE1/Ref-1</i> on adipogenic transcription factor regulation remains unknown. In this study, we investigated the effect of <i>APE1/Ref-1</i> on the regulation of adipocyte differentiation in 3T3-L1 cells. During adipocyte differentiation, <i>APE1/Ref-1</i> expression significantly decreased with the increased expression of adipogenic transcription factors such as CCAAT/enhancer binding protein (<i>C/EBP</i>)-<i>α</i> and peroxisome proliferator-activated receptor (<i>PPAR</i>)-<i>γ</i>, and the adipocyte differentiation marker adipocyte protein 2 (<i>aP2</i>) in a time-dependent manner. However, <i>APE1/Ref-1</i> overexpression inhibited <i>C/EBP-α</i>, <i>PPAR-γ,</i> and <i>aP2</i> expression, which was upregulated during adipocyte differentiation. In contrast, silencing <i>APE1/Ref-1</i> or redox inhibition of <i>APE1/Ref-1</i> using E3330 increased the mRNA and protein levels of <i>C/EBP-α</i>, <i>PPAR-γ</i>, and <i>aP2</i> during adipocyte differentiation. These results suggest that <i>APE1/Ref-1</i> inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting that <i>APE1/Ref-1</i> is a potential therapeutic target for regulating adipocyte differentiation.
ISSN:1661-6596
1422-0067