PMID- 30366059
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 130
DP  - 2019 Jan
TI  - Resveratrol decreases the expression of genes involved in inflammation through 
      transcriptional regulation.
PG  - 8-22
LID - S0891-5849(18)31488-6 [pii]
LID - 10.1016/j.freeradbiomed.2018.10.432 [doi]
AB  - Oxidative stress generated during inflammation is associated with a wide range of 
      pathologies. Resveratrol (RESV) displays anti-inflammatory and antioxidant 
      activities, being a candidate for the development of adjuvant therapies for 
      several inflammatory diseases. Despite this potential, the cellular responses 
      induced by RESV are not well known. In this work, transcriptomic analysis was 
      performed following lipopolysaccharide (LPS) stimulation of monocyte cultures in 
      the presence of RESV. Induction of an inflammatory response was observed after 
      LPS treatment and the addition of RESV led to decreases in expression of the 
      inflammatory mediators, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 
      (IL-8), and monocyte chemoattractant protein-1 (MCP-1), without cytotoxicity. RNA 
      sequencing revealed 823 upregulated and 2098 downregulated genes (cutoff >/=2.0 or 
      </=-2.0) after RESV treatment. Gene ontology analysis showed that the upregulated 
      genes were associated with metabolic processes and the cell cycle, consistent 
      with normal cell growth and differentiation under an inflammatory stimulus. The 
      downregulated genes were associated with inflammatory responses, gene expression, 
      and protein modification. The prediction of master regulators using the iRegulon 
      tool showed nuclear respiratory factor 1 (NRF1) and GA-binding protein alpha 
      subunit (GABPA) as the main regulators of the downregulated genes. Using 
      immunoprecipitation and protein expression assays, we observed that RESV was able 
      to decrease protein acetylation patterns, such as acetylated 
      apurinic/apyrimidinic endonuclease-1/reduction-oxidation factor 1 (APE1/Ref-1), 
      and increase histone methylation. In addition, reductions in p65 (nuclear 
      factor-kappa B (NF-kappaB) subunit) and lysine-specific histone demethylase-1 (LSD1) 
      expression were observed. In conclusion, our data indicate that treatment with 
      RESV caused significant changes in protein acetylation and methylation patterns, 
      suggesting the induction of deacetylase and reduction of demethylase activities 
      that mainly affect regulatory cascades mediated by NF-small ka, CyrillicB and Janus kinase/signal 
      transducers and activators of transcription (JAK/STAT) signaling. NRF1 and GABPA 
      seem to be the main regulators of the transcriptional profile observed after RESV 
      treatment.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Pinheiro, Daniele Maria Lopes
AU  - Pinheiro DML
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - de Oliveira, Ana Helena Sales
AU  - de Oliveira AHS
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil; Chemistry Department, New York University, New 
      York, NY, United States.
FAU - Coutinho, Leonam Gomes
AU  - Coutinho LG
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil; Instituto Federal de Educacao Tecnologica do Rio 
      Grande do Norte, IFRN, Sao Paulo do Potengi, Brazil.
FAU - Fontes, Fabricia Lima
AU  - Fontes FL
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - de Medeiros Oliveira, Rayssa Karla
AU  - de Medeiros Oliveira RK
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - Oliveira, Thais Teixeira
AU  - Oliveira TT
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - Faustino, Andre Luis Fonseca
AU  - Faustino ALF
AD  - Instituto do Cerebro, Universidade Federal do Rio Grande do Norte, Natal, RN, 
      Brazil; Bioinformatics Multidisciplinary Environment (BioME), IMD, UFRN, Brazil.
FAU - Lira da Silva, Vandeclecio
AU  - Lira da Silva V
AD  - Instituto do Cerebro, Universidade Federal do Rio Grande do Norte, Natal, RN, 
      Brazil; Bioinformatics Multidisciplinary Environment (BioME), IMD, UFRN, Brazil.
FAU - de Melo Campos, Julliane Tamara Araujo
AU  - de Melo Campos JTA
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - Lajus, Tirzah Braz Petta
AU  - Lajus TBP
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil.
FAU - de Souza, Sandro Jose
AU  - de Souza SJ
AD  - Instituto do Cerebro, Universidade Federal do Rio Grande do Norte, Natal, RN, 
      Brazil; Bioinformatics Multidisciplinary Environment (BioME), IMD, UFRN, Brazil.
FAU - Agnez-Lima, Lucymara Fassarella
AU  - Agnez-Lima LF
AD  - Departamento de Biologia Celular e Genetica, Universidade Federal do Rio Grande 
      do Norte, UFRN, Natal, Brazil. Electronic address: lfagnez@ufrnet.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (GA-Binding Protein Transcription Factor)
RN  - 0 (GABPA protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NRF1 protein, human)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Acetylation
MH  - Anti-Inflammatory Agents/*metabolism
MH  - Antioxidants/*metabolism
MH  - Cytokines/metabolism
MH  - GA-Binding Protein Transcription Factor/genetics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Gene Ontology
MH  - Humans
MH  - Inflammation/*genetics
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Monocytes/*immunology
MH  - NF-kappa B/metabolism
MH  - Nuclear Respiratory Factor 1/genetics
MH  - Oxidative Stress
MH  - Resveratrol/*metabolism
MH  - Sequence Analysis, RNA
MH  - Signal Transduction
MH  - U937 Cells
OTO - NOTNLM
OT  - Chromatin
OT  - Inflammation
OT  - RNAseq
OT  - Resveratrol
OT  - Transcription
EDAT- 2018/10/27 06:00
MHDA- 2020/02/18 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/08/27 00:00 [received]
PHST- 2018/10/18 00:00 [revised]
PHST- 2018/10/18 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - S0891-5849(18)31488-6 [pii]
AID - 10.1016/j.freeradbiomed.2018.10.432 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2019 Jan;130:8-22. doi: 10.1016/j.freeradbiomed.2018.10.432. 
      Epub 2018 Oct 24.