RGD Reference Report - Multiple retinol and retinal dehydrogenases catalyze all-trans-retinoic acid biosynthesis in astrocytes. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Multiple retinol and retinal dehydrogenases catalyze all-trans-retinoic acid biosynthesis in astrocytes.

Authors: Wang, C  Kane, MA  Napoli, JL 
Citation: Wang C, etal., J Biol Chem. 2011 Feb 25;286(8):6542-53. Epub 2010 Dec 7.
RGD ID: 6771354
Pubmed: (View Article at PubMed) PMID:21138835
DOI: Full-text: DOI:10.1074/jbc.M110.198382

All-trans-retinoic acid (atRA) stimulates neurogenesis, dendritic growth of hippocampal neurons, and higher cognitive functions, such as spatial learning and memory formation. Although astrocyte-derived atRA has been considered a key factor in neurogenesis, little direct evidence identifies hippocampus cell types and the enzymes that biosynthesize atRA. Here we show that primary rat astrocytes, but not neurons, biosynthesize atRA using multiple retinol dehydrogenases (Rdh) of the short chain dehydrogenase/reductase gene family and retinaldehyde dehydrogenases (Raldh). Astrocytes secrete atRA into their medium; neurons sequester atRA. The first step, conversion of retinol into retinal, is rate-limiting. Neurons and astrocytes both synthesize retinyl esters and reduce retinal into retinol. siRNA knockdown indicates that Rdh10, Rdh2 (mRdh1), and Raldh1, -2, and -3 contribute to atRA production. Knockdown of the Rdh Dhrs9 increased atRA synthesis approximately 40% by increasing Raldh1 expression. Immunocytochemistry revealed cytosolic and nuclear expression of Raldh1 and cytosol and perinuclear expression of Raldh2. atRA autoregulated its concentrations by inducing retinyl ester synthesis via lecithin:retinol acyltransferase and stimulating its catabolism via inducing Cyp26B1. These data show that adult hippocampus astrocytes rely on multiple Rdh and Raldh to provide a paracrine source of atRA to neurons, and atRA regulates its own biosynthesis in astrocytes by directing flux of retinol. Observation of cross-talk between Dhrs9 and Raldh1 provides a novel mechanism of regulating atRA biosynthesis.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Aldh1a1  (aldehyde dehydrogenase 1 family, member A1)
Aldh1a2  (aldehyde dehydrogenase 1 family, member A2)
Aldh1a3  (aldehyde dehydrogenase 1 family, member A3)
Cyp26b1  (cytochrome P450, family 26, subfamily b, polypeptide 1)
Dhrs9  (dehydrogenase/reductase 9)
Rdh10  (retinol dehydrogenase 10)
Rdh16  (retinol dehydrogenase 16)

Genes (Mus musculus)
Aldh1a1  (aldehyde dehydrogenase family 1, subfamily A1)
Aldh1a2  (aldehyde dehydrogenase family 1, subfamily A2)
Aldh1a3  (aldehyde dehydrogenase family 1, subfamily A3)
Cyp26b1  (cytochrome P450, family 26, subfamily b, polypeptide 1)
Dhrs9  (dehydrogenase/reductase (SDR family) member 9)
Rdh1  (retinol dehydrogenase 1 (all trans))
Rdh10  (retinol dehydrogenase 10 (all-trans))

Genes (Homo sapiens)
ALDH1A1  (aldehyde dehydrogenase 1 family member A1)
ALDH1A2  (aldehyde dehydrogenase 1 family member A2)
ALDH1A3  (aldehyde dehydrogenase 1 family member A3)
CYP26B1  (cytochrome P450 family 26 subfamily B member 1)
DHRS9  (dehydrogenase/reductase 9)
RDH10  (retinol dehydrogenase 10)


Additional Information