Makoto Kurano1, Masumi Hara2, Takahiro Nojiri3, Hitoshi Ikeda1,3, Kazuhisa Tsukamoto4, Yutaka Yatomi1,3. 1. Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 2. Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan. 3. Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. 4. Department of Metabolism, Diabetes and Nephrology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan.
Abstract
BACKGROUND AND PURPOSE: Resveratrol exerts a range of beneficial actions in several areas of pathophysiology, including vascular biology. Here, we have investigated the effects of resveratrol on apolipoprotein M (apoM), a carrier and modulator of sphingosine 1-phosphate (S1P), a vasoactive lipid mediator. EXPERIMENTAL APPROACH: We used a hepatoma cell line (HepG2), human primary hepatocytes and C57BL/6 mice. We measured apoM, S1P and related enzymes, LDL receptors and sirtuin1 activity, using Western blotting, RT-PCR and enzyme assays. We also used si-RNA to knock-down sirtuin1 in HepG2 cells. KEY RESULTS: In cultures of HepG2 cells, resveratrol (1-10 μM) increased intracellular apoM and S1P. High concentrations of resveratrol (100 μM) decreased extracellular (in the culture medium) apoM, whereas moderate concentrations of resveratrol (1-10 μM) increased extracellular apoM. High concentrations of resveratrol also increased LDL receptor expression, while all concentrations of resveratrol activated the histone deacetylase sirtuin1. In cultures of human primary hepatocytes, resveratrol, at all concentrations, increased both intra- and extracellular apoM. When wild-type mice were fed a resveratrol-containing chow (0.3% w/w) for 2 weeks, both the plasma and hepatic apoM and S1P levels were increased. However, the resveratrol diet did not affect hepatic LDL receptor levels in this in vivo study. CONCLUSIONS AND IMPLICATIONS: Resveratrol increased intra- and extracellular levels of apoM, along with intracellular S1P levels, while a high concentration of resveratrol reduced extracellular apoM. The present findings suggest that resveratrol has novel effects on the metabolic kinetics of S1P, a multi-functional bioactive phospholipid.
BACKGROUND AND PURPOSE:Resveratrol exerts a range of beneficial actions in several areas of pathophysiology, including vascular biology. Here, we have investigated the effects of resveratrol on apolipoprotein M (apoM), a carrier and modulator of sphingosine 1-phosphate (S1P), a vasoactive lipid mediator. EXPERIMENTAL APPROACH: We used a hepatoma cell line (HepG2), human primary hepatocytes and C57BL/6 mice. We measured apoM, S1P and related enzymes, LDL receptors and sirtuin1 activity, using Western blotting, RT-PCR and enzyme assays. We also used si-RNA to knock-down sirtuin1 in HepG2 cells. KEY RESULTS: In cultures of HepG2 cells, resveratrol (1-10 μM) increased intracellular apoM and S1P. High concentrations of resveratrol (100 μM) decreased extracellular (in the culture medium) apoM, whereas moderate concentrations of resveratrol (1-10 μM) increased extracellular apoM. High concentrations of resveratrol also increased LDL receptor expression, while all concentrations of resveratrol activated the histone deacetylase sirtuin1. In cultures of human primary hepatocytes, resveratrol, at all concentrations, increased both intra- and extracellular apoM. When wild-type mice were fed a resveratrol-containing chow (0.3% w/w) for 2 weeks, both the plasma and hepatic apoM and S1P levels were increased. However, the resveratrol diet did not affect hepatic LDL receptor levels in this in vivo study. CONCLUSIONS AND IMPLICATIONS: Resveratrol increased intra- and extracellular levels of apoM, along with intracellular S1P levels, while a high concentration of resveratrol reduced extracellular apoM. The present findings suggest that resveratrol has novel effects on the metabolic kinetics of S1P, a multi-functional bioactive phospholipid.
Authors: E Calleri; G Pochetti; K S S Dossou; A Laghezza; R Montanari; D Capelli; E Prada; F Loiodice; G Massolini; M Bernier; R Moaddel Journal: Chembiochem Date: 2014-05-05 Impact factor: 3.164
Authors: Maria L Allende; Teiji Sasaki; Hiromichi Kawai; Ana Olivera; Yide Mi; Gerhild van Echten-Deckert; Richard Hajdu; Mark Rosenbach; Carol Ann Keohane; Suzanne Mandala; Sarah Spiegel; Richard L Proia Journal: J Biol Chem Date: 2004-09-30 Impact factor: 5.157
Authors: Brent A Wilkerson; G Daniel Grass; Shane B Wing; W Scott Argraves; Kelley M Argraves Journal: J Biol Chem Date: 2012-11-07 Impact factor: 5.157
Authors: Kelley M Argraves; Amar A Sethi; Patrick J Gazzolo; Brent A Wilkerson; Alan T Remaley; Anne Tybjaerg-Hansen; Børge G Nordestgaard; Sharon D Yeatts; Katherine S Nicholas; Jeremy L Barth; W Scott Argraves Journal: Lipids Health Dis Date: 2011-05-09 Impact factor: 3.876
Authors: Guilherme Felipe Santos Fernandes; Gabriel Dalio Bernardes Silva; Aline Renata Pavan; Diego Eidy Chiba; Chung Man Chin; Jean Leandro Dos Santos Journal: Nutrients Date: 2017-11-01 Impact factor: 5.717