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 AMPKα which is regulated by SIRT6, increased. In this study, we examined the mechanism underlying cholesterol regulation by fluvastatin via SREBP-1 and AMPKα pathway and suggested that fluvastatin is an SIRT6 activator that regulates cholesterol homeostasis and fatty liver disease.
| Original language | English |
|---|---|
| Pages (from-to) | 1415-1421 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 503 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2018 Sep 10 |
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Keywords
- AMP-Activated protein kinaseα
- Fluvastatin
- Nonalcoholic fatty liver disease
- SIRT6
- SREBP-1
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells. / Kim, Ji Hye; Lee, Jun Mi; Kim, Jong-Hoon; Kim, Kwang Rok.
In: Biochemical and Biophysical Research Communications, Vol. 503, No. 3, 10.09.2018, p. 1415-1421.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells
AU - Kim, Ji Hye
AU - Lee, Jun Mi
AU - Kim, Jong-Hoon
AU - Kim, Kwang Rok
PY - 2018/9/10
Y1 - 2018/9/10
N2 - 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 AMPKα which is regulated by SIRT6, increased. In this study, we examined the mechanism underlying cholesterol regulation by fluvastatin via SREBP-1 and AMPKα pathway and suggested that fluvastatin is an SIRT6 activator that regulates cholesterol homeostasis and fatty liver disease.
AB - 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 AMPKα which is regulated by SIRT6, increased. In this study, we examined the mechanism underlying cholesterol regulation by fluvastatin via SREBP-1 and AMPKα pathway and suggested that fluvastatin is an SIRT6 activator that regulates cholesterol homeostasis and fatty liver disease.
KW - AMP-Activated protein kinaseα
KW - Fluvastatin
KW - Nonalcoholic fatty liver disease
KW - SIRT6
KW - SREBP-1
UR - http://www.scopus.com/inward/record.url?scp=85050851678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050851678&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2018.07.057
DO - 10.1016/j.bbrc.2018.07.057
M3 - Article
C2 - 30078674
AN - SCOPUS:85050851678
VL - 503
SP - 1415
EP - 1421
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -