EurekaMag
+ Translate
+ Most Popular
Gaucher's disease;thirty-two years experience at Siriraj Hospital
A study of Macrobathra Meyrick from China (Lepidoptera, Cosmopterigidae)
First occurrence in ores of tetragonal chalcocite
Effects of trace element nutrition on sleep patterns in adult women
N.Z. range management guidelines. 2. Design of grazing management systems for tussock country
A case of lipoma of the esophagus
A revision of world Acanthosomatidae (Heteroptera: Pentatomidae): keys to and descriptions of subfamilies, tribes and genera, with designation of types
Life history of the coronate scyphozoan Linuche unguiculata (Swartz, 1788)
Perceptual restoration of obliterated sounds
Mutagenicity studies on two chromium(III) coordination compounds
The formation of the skeleton. I. Growth of a long bone. 1st appearance of a center of calcification
Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis
The joint commission: four key root causes loom large in sentinel event data
Treatment of vitiligo with topical 15% lactic acid solution in combination with ultra violet-A
Behaviour of dairy cows within three hours after feed supply: I. Influence of housing type and time elapsing after feed supply
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS)
The diet composition and nutritional knowledge of patients with anorexia nervosa
Physoporella croatica Herak, 1958 of the Slovak karst Anisian (Slovakia, the West Carpathians Mts.)
Bright lights, big noise. How effective are vehicle warning systems?
Ein Plesiosaurier-Rest mit Magensteinen aus mittlerem Lias von Quedlinburg
Incidence of Chlamydia trachomatis in patients with sterility
Monster soup: the microscope and Victorian fantasy
Preliminary tests with residual sprays against poultry lice
Duration of the life of plants in phylogeny

Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells


Fluvastatin activates sirtuin 6 to regulate sterol regulatory element-binding proteins and AMP-activated protein kinase in HepG2 cells



Biochemical and Biophysical Research Communications 503(3): 1415-1421



ISSN/ISBN: 0006-291X

PMID: 30078674

DOI: 10.1016/j.bbrc.2018.07.057

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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 065156954

Download citation: RISBibTeXText

Related references

P75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3. Journal of Biological Chemistry 291(20): 10747-10758, 2016

Olea europaea Linn (Oleaceae) Fruit Pulp Extract Suppresses Sterol Regulatory Element-Binding Proteins-1c via AMP-Activated Protein Kinase Activation in Human Hepatic Cells. Tropical Journal of Pharmaceutical Research 13(8): 1265-1271, 2014

Overexpression of A-kinase anchoring protein 12A activates sterol regulatory element binding protein-2 and enhances cholesterol efflux in hepatic cells. International Journal of Biochemistry and Cell Biology 40(11): 2534-2543, 2008

AMP-activated protein kinase suppresses LXR-dependent sterol regulatory element-binding protein-1c transcription in rat hepatoma McA-RH7777 cells. Journal of Cellular Biochemistry 106(3): 414-426, 2009

Ixeris dentata (Thunb) Nakai Ethylacetate Extract Attenuates Sterol Regulatory Element-Binding Proteins-1c via AMP-Activated Protein Kinase Activation. Tropical Journal of Pharmaceutical Research 15(3): 453-459, 2016

Metformin attenuates palmitic acid-induced insulin resistance in L6 cells through the AMP-activated protein kinase/sterol regulatory element-binding protein-1c pathway. International Journal of Molecular Medicine 35(6): 1734-1740, 2015

P38 mitogen-activated protein kinase and liver X receptor-α mediate the leptin effect on sterol regulatory element binding protein-1c expression in hepatic stellate cells. Molecular Medicine 18: 10-18, 2012

Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway. Molecular Endocrinology 15(10): 1817-1828, 2001

Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal S6 kinase signaling pathway. Hepatology Research: the Official Journal of the Japan Society of Hepatology 47(7): 683-701, 2017

Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins. Biochimica et Biophysica Acta 1821(10): 1350-1360, 2012

Apoptosis-induced release of mature sterol regulatory element-binding proteins activates sterol-responsive genes. Journal of Lipid Research 42(12): 1939-1946, 2001

Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma. Journal of Biological Chemistry 293(17): 6623-6634, 2018

Dehydroepiandrosterone activates cyclic adenosine 3',5'-monophosphate/protein kinase A signalling and suppresses sterol regulatory element-binding protein-1 expression in cultured primary chicken hepatocytes. British Journal of Nutrition 102(5): 680-686, 2009

Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase/sterol regulatory element-binding protein 1 signaling in mice. Hepatology 55(2): 437-446, 2012

Docosahexaenoic acid inhibits proteolytic processing of sterol regulatory element-binding protein-1c (SREBP-1c) via activation of AMP-activated kinase. Biochimica et Biophysica Acta 1851(12): 1521-1529, 2015