Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors.

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German OL, Monaco S, Agnolazza DL, Rotstein NP, Politi LE

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors.

J Lipid Res. 2013 Aug;54(8):2236-46. doi: 10.1194/jlr.M039040. Epub 2013 May 30.

PubMed ID

23723389 [ View in PubMed

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Abstract

We have established that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, promotes survival of rat retina photoreceptors during early development in vitro and upon oxidative stress by activating the ERK/MAPK signaling pathway. Here we have investigated whether DHA turns on this pathway through activation of retinoid X receptors (RXRs) or by inducing tyrosine kinase (Trk) receptor activation. We also evaluated whether DHA release from phospholipids was required for its protective effect. Addition of RXR antagonists (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during early development in vitro and upon oxidative stress induced with Paraquat or H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of photoreceptor apoptosis. These results imply that activation of RXRs was required for DHA protection whereas Trk receptors were not involved in this protection. Pretreatment with 4-bromoenol lactone, a phospholipase A2 inhibitor, blocked DHA prevention of oxidative stress-induced apoptosis of photoreceptors. It is noteworthy that RXR agonists (HX630, PA024) also rescued photoreceptors from H2O2-induced apoptosis. These results provide the first evidence that activation of RXRs prevents photoreceptor apoptosis and suggest that DHA is first released from phospholipids and then activates RXRs to promote the survival of photoreceptors.

DrugBank Data that Cites this Article

Drugs

Doconexent

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Doconexent	Retinoic acid receptor RXR-alpha	Protein	Humans	Yes	Activator	Details
Doconexent	Retinoic acid receptor RXR-beta	Protein	Humans	Yes	Activator	Details
Doconexent	Retinoic acid receptor RXR-gamma	Protein	Humans	Yes	Activator	Details