Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells
- Authors
- Kim, Ji-Hye; Lee, Jun Mi; Kim, Jong-Hoon; Kim, Kwang Rok
- Issue Date
- 10-9월-2018
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- SIRT6; Fluvastatin; SREBP-1; AMP-Activated protein kinase alpha; Nonalcoholic fatty liver disease
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.503, no.3, pp.1415 - 1421
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 503
- Number
- 3
- Start Page
- 1415
- End Page
- 1421
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/73116
- DOI
- 10.1016/j.bbrc.2018.07.057
- ISSN
- 0006-291X
- Abstract
- Sirtuins, a family of NAD(+)-dependent deacetylase enzymes, have been identified as mammalian homologs of yeast silent information regulator 2 (SIR2). Sirtuin 6 (SIRT6) plays important roles in cell homeostasis, DNA damage repair, cancer suppression, and aging. SIRT6 overexpression improves metabolic diseases, such as hypercholesterolemia, cholesterol-related disease, and type 2 diabetes via AMP-activated protein kinase (AMPK) activation. SIRT6 is abundant in the liver and is a crucial target for patients with liver steatosis. Compounds for drug repositioning were screened to identify potential SIRT6 activators, and fluvastatin, a synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase that reduces cholesterol synthesis, was identified to activate SIRT6. When HepG2 cells were treated with fluvastatin, the expression of SIRT6 and phosphorylation of sterol regulatory element-binding protein (SREBP)-1 and AMPK alpha, which is regulated by SIRT6, increased. In this study, we examined the mechanism underlying cholesterol regulation by fluvastatin via SREBP-1 and AMPK alpha pathway and suggested that fluvastatin is an SIRT6 activator that regulates cholesterol homeostasis and fatty liver disease. (C) 2018 Elsevier Inc. All rights reserved.
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