The flavonoid derivative 4′-nitro-6-hydroxyflavone suppresses the activity of HNF4α and stimulates the degradation of HNF4α protein through the activation of AMPK*. Issue 8 (3rd August 2017)

• Record Type: Journal Article
• Authors: Inoue, Jun; Ikeda, Shiori; Kanayama, Tomohiko; Sato, Ryuichiro
• Is Part Of: Bioscience, biotechnology, and biochemistry. Volume 81:Issue 8(2017)
• Page Start: 1548
• Page End: 1552
• Publication Date: 2017-08-03
• Subjects: AMPK -- HNF4α -- flavonoid; Biotechnology -- Periodicals; Biochemistry -- Periodicals; 660.6
• DOI: 10.1080/09168451.2017.1325316
• Languages: English
• ISSNs: 0916-8451

Abstract

Abstract : Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor that regulates the expression of genes involved in a number of critical metabolic pathways. The modulation of HNF4α activity is thought to be a promising drug target pathway for hyperlipidemia. To identify compounds that reduce the activity of HNF4α, we conducted luciferase reporter assays using the promoter region of microsomal triglyceride transfer protein (MTP) gene, which contains an HNF4α-responsive element. Using this system, we show here that the flavonoid derivative 4′-nitro-6-hydroxyflavone (NOHF) suppresses MTP promoter activity. Treatment with NOHF caused a decrease in the expression of the HNF4α target gene. We also identified that NOHF triggers the AMP-activated protein kinase (AMPK) and accelerates the degradation of HNF4α protein. Knock-down of AMPK diminishes the effect of NOHF. These results indicate that NOHF is an AMPK activator and attenuates the transcriptional activity of HNF4α, at least in part, by accelerating HNF4α protein degradation. Abstract :