PMID- 33065288
OWN - NLM
STAT- MEDLINE
DCOM- 20210413
LR  - 20210413
IS  - 1879-2618 (Electronic)
IS  - 1388-1981 (Linking)
VI  - 1866
IP  - 1
DP  - 2021 Jan
TI  - Inhibition of alcohol-induced inflammation and oxidative stress by astaxanthin is 
      mediated by its opposite actions in the regulation of sirtuin 1 and histone 
      deacetylase 4 in macrophages.
PG  - 158838
LID - S1388-1981(20)30230-4 [pii]
LID - 10.1016/j.bbalip.2020.158838 [doi]
AB  - We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, 
      repressed ethanol-induced inflammation and oxidative stress in macrophages. We 
      explored the role of sirtuin 1 (SIRT1) and histone deacetylase 4 (HDAC4) in the 
      inhibitory effect of ASTX on inflammation and oxidative stress in macrophages 
      exposed to ethanol. Ethanol decreased mRNA and protein of SIRT1 while increasing 
      those of HDAC4, which was attenuated by ASTX in RAW 264.7 macrophages and mouse 
      bone marrow-derived macrophages (BMDMs). Inhibition of SIRT1 expression or 
      activity augmented ethanol-induced Hdac4 expression, but SIRT1 activation 
      elicited the opposite effect. Consistently, Hdac4 knockdown increased Sirt1 
      expression with decreases in ethanol-induced inflammatory gene expression, but 
      its overexpression resulted in the opposite effects. Furthermore, BMDMs from mice 
      with macrophage specific-deletion of Hdac4 (Hdac4(MKO)) showed significant 
      decreases in ethanol-induced inflammatory genes and ROS accumulation but an 
      increase in Sirt1 expression. Macrophage specific deletion of Hdac4 or ASTX 
      abolished the changes in genes for mitochondrial biogenesis and glycolysis by 
      ethanol. Ethanol increased mitochondrial respiration, ATP production, and proton 
      leak, but decreased maximal respiration and spare respiratory capacity, all of 
      which were abolished by ASTX in RAW 264.7 macrophages. The ethanol-induced 
      alterations in mitochondrial respiration were abrogated in Hdac4(MKO) BMDMs. In 
      conclusion, the anti-inflammatory and antioxidant properties of ASTX in 
      ethanol-treated macrophages may be mediated, at least partly, by its opposite 
      effect on SIRT1 and HDAC4 to empower SIRT1 to counteract ethanol-induced 
      activation of HDAC4.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Kang, Hyunju
AU  - Kang H
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, 
      USA.
FAU - Park, Young-Ki
AU  - Park YK
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, 
      USA.
FAU - Lee, Ji-Young
AU  - Lee JY
AD  - Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, 
      USA. Electronic address: ji-young.lee@uconn.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201013
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Biol Lipids
JT  - Biochimica et biophysica acta. Molecular and cell biology of lipids
JID - 101731727
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Xanthophylls)
RN  - 3K9958V90M (Ethanol)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 8XPW32PR7I (astaxanthine)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.5.1.98 (Hdac5 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Ethanol/*antagonists & inhibitors/pharmacology
MH  - Gene Expression Regulation
MH  - Glycolysis/drug effects/genetics
MH  - Histone Deacetylases/*genetics/metabolism
MH  - Inflammation
MH  - Macrophages/cytology/*drug effects/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/drug effects/genetics/metabolism
MH  - Organelle Biogenesis
MH  - Oxidative Phosphorylation/drug effects
MH  - Oxidative Stress
MH  - Primary Cell Culture
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/agonists/antagonists & inhibitors/metabolism
MH  - Sirtuin 1/*genetics/metabolism
MH  - Xanthophylls/pharmacology
OTO - NOTNLM
OT  - Alcohol
OT  - Astaxanthin
OT  - Histone deacetylase 4
OT  - Inflammation
OT  - Macrophage
OT  - Sirtuin 1
EDAT- 2020/10/17 06:00
MHDA- 2021/04/14 06:00
CRDT- 2020/10/16 20:11
PHST- 2020/06/15 00:00 [received]
PHST- 2020/09/25 00:00 [revised]
PHST- 2020/10/07 00:00 [accepted]
PHST- 2020/10/17 06:00 [pubmed]
PHST- 2021/04/14 06:00 [medline]
PHST- 2020/10/16 20:11 [entrez]
AID - S1388-1981(20)30230-4 [pii]
AID - 10.1016/j.bbalip.2020.158838 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Jan;1866(1):158838. doi: 
      10.1016/j.bbalip.2020.158838. Epub 2020 Oct 13.