PMID- 31046795
OWN - NLM
STAT- MEDLINE
DCOM- 20200410
LR  - 20200410
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 17
IP  - 1
DP  - 2019 May 2
TI  - Genomic and non-genomic pathways are both crucial for peak induction of neurite 
      outgrowth by retinoids.
PG  - 40
LID - 10.1186/s12964-019-0352-4 [doi]
LID - 40
AB  - Retinoic acid (RA) is the active metabolite of vitamin A and essential for many 
      physiological processes, particularly the induction of cell differentiation. In 
      addition to regulating genomic transcriptional activity via RA receptors (RARs) 
      and retinoid X receptors (RXRs), non-genomic mechanisms of RA have been 
      described, including the regulation of ERK1/2 kinase phosphorylation, but are 
      poorly characterised. In this study, we test the hypothesis that genomic and 
      non-genomic mechanisms of RA are regulated independently with respect to the 
      involvement of ligand-dependent RA receptors. A panel of 28 retinoids (compounds 
      with vitamin A-like activity) showed a marked disparity in genomic (gene 
      expression) versus non-genomic (ERK1/2 phosphorylation) assays. These results 
      demonstrate that the capacity of a compound to activate gene transcription does 
      not necessarily correlate with its ability to regulate a non-genomic activity 
      such as ERK 1/2 phosphorylation. Furthermore, a neurite outgrowth assay indicated 
      that retinoids that could only induce either genomic, or non-genomic activities, 
      were not strong promoters of neurite outgrowth, and that activities with respect 
      to both transcriptional regulation and ERK1/2 phosphorylation produced maximum 
      neurite outgrowth. These results suggest that the development of effective 
      retinoids for clinical use will depend on the selection of compounds which have 
      maximal activity in non-genomic as well as genomic assays.
FAU - Khatib, Thabat
AU  - Khatib T
AD  - School of Medicine, Medical Sciences and Nutrition, Institute of Medical 
      Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.
FAU - Marini, Pietro
AU  - Marini P
AD  - School of Medicine, Medical Sciences and Nutrition, Institute of Medical 
      Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.
FAU - Nunna, Sudheer
AU  - Nunna S
AD  - School of Medicine, Medical Sciences and Nutrition, Institute of Medical 
      Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.
FAU - Chisholm, David R
AU  - Chisholm DR
AD  - Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
FAU - Whiting, Andrew
AU  - Whiting A
AD  - Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
FAU - Redfern, Christopher
AU  - Redfern C
AD  - Northern Institute for Cancer Research, Medical School, Newcastle University, 
      Newcastle upon Tyne, NE2 4HH, UK.
FAU - Greig, Iain R
AU  - Greig IR
AD  - School of Medicine, Medical Sciences and Nutrition, Institute of Medical 
      Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.
FAU - McCaffery, Peter
AU  - McCaffery P
AUID- ORCID: 0000-0002-5956-3997
AD  - School of Medicine, Medical Sciences and Nutrition, Institute of Medical 
      Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK. 
      p.j.mccaffery@abdn.ac.uk.
LA  - eng
GR  - BB/P004806/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190502
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Neuronal Outgrowth/*drug effects
MH  - Receptors, Retinoic Acid/genetics/metabolism
MH  - Retinoids/*pharmacology
MH  - *Transcriptome
PMC - PMC6498645
OTO - NOTNLM
OT  - Erk1/2
OT  - Neurite outgrowth
OT  - Non-genomic
OT  - RAR
OT  - Retinoic acid
OT  - Transcription
OT  - Vitamin a
COIS- AUTHORS' INFORMATION: Not applicable ETHICS APPROVAL: Animal use: All procedures 
      conformed to Home Office regulations and local ethics committee guidelines. 
      CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare 
      that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains 
      neutral with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2019/05/03 06:00
MHDA- 2020/04/11 06:00
PMCR- 2019/05/02
CRDT- 2019/05/04 06:00
PHST- 2019/01/08 00:00 [received]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/05/04 06:00 [entrez]
PHST- 2019/05/03 06:00 [pubmed]
PHST- 2020/04/11 06:00 [medline]
PHST- 2019/05/02 00:00 [pmc-release]
AID - 10.1186/s12964-019-0352-4 [pii]
AID - 352 [pii]
AID - 10.1186/s12964-019-0352-4 [doi]
PST - epublish
SO  - Cell Commun Signal. 2019 May 2;17(1):40. doi: 10.1186/s12964-019-0352-4.