9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice

Ralph Rühl, Agnieszka Krzyżosiak, Anna Niewiadomska-Cimicka, Natacha Rochel, Lajos Szeles, Belén Vaz, Marta Wietrzych-Schindler, Susana Álvarez, Monika Szklenar, Laszlo Nagy, Angel R. de Lera, Wojciech Krężel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere1005213
JournalPLoS Genetics
Volume11
Issue number6
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Retinoid X Receptors
retinoids
Retinoids
ligand
Ligands
receptors
acids
acid
mice
Cellular Retinol-Binding Proteins
Physiological Phenomena
retinol-binding protein
Memory Disorders
hormone
Cytoplasmic and Nuclear Receptors
13,14-dihydroretinoic acid
ligands
phenotype
hormone receptors
Dendritic Cells

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Rühl, R., Krzyżosiak, A., Niewiadomska-Cimicka, A., Rochel, N., Szeles, L., Vaz, B., ... Krężel, W. (2015). 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice. PLoS Genetics, 11(6), [e1005213]. https://doi.org/10.1371/journal.pgen.1005213

9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice. / Rühl, Ralph; Krzyżosiak, Agnieszka; Niewiadomska-Cimicka, Anna; Rochel, Natacha; Szeles, Lajos; Vaz, Belén; Wietrzych-Schindler, Marta; Álvarez, Susana; Szklenar, Monika; Nagy, Laszlo; de Lera, Angel R.; Krężel, Wojciech.

In: PLoS Genetics, Vol. 11, No. 6, e1005213, 01.01.2015.

Research output: Contribution to journalArticle

Rühl, R, Krzyżosiak, A, Niewiadomska-Cimicka, A, Rochel, N, Szeles, L, Vaz, B, Wietrzych-Schindler, M, Álvarez, S, Szklenar, M, Nagy, L, de Lera, AR & Krężel, W 2015, '9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice', PLoS Genetics, vol. 11, no. 6, e1005213. https://doi.org/10.1371/journal.pgen.1005213
Rühl R, Krzyżosiak A, Niewiadomska-Cimicka A, Rochel N, Szeles L, Vaz B et al. 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice. PLoS Genetics. 2015 Jan 1;11(6). e1005213. https://doi.org/10.1371/journal.pgen.1005213
Rühl, Ralph ; Krzyżosiak, Agnieszka ; Niewiadomska-Cimicka, Anna ; Rochel, Natacha ; Szeles, Lajos ; Vaz, Belén ; Wietrzych-Schindler, Marta ; Álvarez, Susana ; Szklenar, Monika ; Nagy, Laszlo ; de Lera, Angel R. ; Krężel, Wojciech. / 9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice. In: PLoS Genetics. 2015 ; Vol. 11, No. 6.
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