PMID- 26030625
OWN - NLM
STAT- MEDLINE
DCOM- 20160610
LR  - 20191210
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 11
IP  - 6
DP  - 2015 Jun
TI  - 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand 
      in Mice.
PG  - e1005213
LID - 10.1371/journal.pgen.1005213 [doi]
LID - e1005213
AB  - The retinoid X receptors (RXRs) are ligand-activated transcription factors which 
      heterodimerize with a number of nuclear hormone receptors, thereby controlling a 
      variety of (patho)-physiological processes. Although synthetic RXR ligands are 
      developed for the treatment of various diseases, endogenous ligand(s) for these 
      receptors have not been conclusively identified. We show here that mice lacking 
      cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting 
      compromised RXR signaling. Using HPLC-MS and chemical synthesis we identified in 
      Rbp1-/- mice reduced levels of 9-cis-13,14-dihydroretinoic acid (9CDHRA), which 
      acts as an RXR ligand since it binds and transactivates RXR in various assays. 
      9CDHRA rescues the Rbp1-/- phenotype similarly to a synthetic RXR ligand and 
      displays similar transcriptional activity in cultured human dendritic cells. High 
      endogenous levels of 9CDHRA in mice indicate physiological relevance of these 
      data and that 9CDHRA acts as an endogenous RXR ligand.
FAU - Ruhl, Ralph
AU  - Ruhl R
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, Debrecen, 
      Hungary; Paprika Bioanalytics BT, Debrecen, Hungary.
FAU - Krzyzosiak, Agnieszka
AU  - Krzyzosiak A
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France; Inserm, U 964; CNRS UMR 7104, Universite de Strasbourg, Strasbourg, 
      France.
FAU - Niewiadomska-Cimicka, Anna
AU  - Niewiadomska-Cimicka A
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France; Inserm, U 964; CNRS UMR 7104, Universite de Strasbourg, Strasbourg, 
      France.
FAU - Rochel, Natacha
AU  - Rochel N
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France; Inserm, U 964; CNRS UMR 7104, Universite de Strasbourg, Strasbourg, 
      France.
FAU - Szeles, Lajos
AU  - Szeles L
AD  - DE-MTA "Lendulet" Immunogenomics Research Group, University of Debrecen, 
      Debrecen, Hungary.
FAU - Vaz, Belen
AU  - Vaz B
AD  - Departamento de Quimica Organica and CINBIO, Facultad de Quimica, Universidade de 
      Vigo, Vigo, Spain; Instituto de Investigacion Biomedica de Vigo (IBIV), Vigo, 
      Spain.
FAU - Wietrzych-Schindler, Marta
AU  - Wietrzych-Schindler M
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France; Inserm, U 964; CNRS UMR 7104, Universite de Strasbourg, Strasbourg, 
      France.
FAU - Alvarez, Susana
AU  - Alvarez S
AD  - Departamento de Quimica Organica and CINBIO, Facultad de Quimica, Universidade de 
      Vigo, Vigo, Spain; Instituto de Investigacion Biomedica de Vigo (IBIV), Vigo, 
      Spain.
FAU - Szklenar, Monika
AU  - Szklenar M
AD  - Paprika Bioanalytics BT, Debrecen, Hungary.
FAU - Nagy, Laszlo
AU  - Nagy L
AD  - DE-MTA "Lendulet" Immunogenomics Research Group, University of Debrecen, 
      Debrecen, Hungary.
FAU - de Lera, Angel R
AU  - de Lera AR
AD  - Departamento de Quimica Organica and CINBIO, Facultad de Quimica, Universidade de 
      Vigo, Vigo, Spain; Instituto de Investigacion Biomedica de Vigo (IBIV), Vigo, 
      Spain.
FAU - Krezel, Wojciech
AU  - Krezel W
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France; Inserm, U 964; CNRS UMR 7104, Universite de Strasbourg, Strasbourg, 
      France.
LA  - eng
SI  - GEO/GSE48573
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150601
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (13,14-dihydroretinoic acid)
RN  - 0 (Ligands)
RN  - 0 (Rbp1 protein, mouse)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinol-Binding Proteins, Cellular)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Humans
MH  - Ligands
MH  - Memory Disorders/*genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Retinoid X Receptors/chemistry/genetics/*metabolism
MH  - Retinol-Binding Proteins, Cellular/genetics/metabolism
MH  - Tretinoin/*analogs & derivatives/metabolism
PMC - PMC4451509
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: RR is owner of Paprika Bioanalytics BT; RR and MS 
      are employees of Paprika Bioanalytics BT; WK, RR and ARdL are inventors on the 
      patent for synthesis and biomedical applications of 9CDHRA.
EDAT- 2015/06/02 06:00
MHDA- 2016/06/11 06:00
PMCR- 2015/06/01
CRDT- 2015/06/02 06:00
PHST- 2014/10/24 00:00 [received]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/06/02 06:00 [entrez]
PHST- 2015/06/02 06:00 [pubmed]
PHST- 2016/06/11 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - PGENETICS-D-14-02811 [pii]
AID - 10.1371/journal.pgen.1005213 [doi]
PST - epublish
SO  - PLoS Genet. 2015 Jun 1;11(6):e1005213. doi: 10.1371/journal.pgen.1005213. 
      eCollection 2015 Jun.