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

German, Olga Lorena; Monaco, Sandra; Agnolazza, Daniela L.; Rotstein, Nora P.; Politi, Luis E.

doi:10.1194/jlr.m039040

Cited by 40 publications

(47 citation statements)

References 63 publications

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“…Insulin-like growth factor binding protein (IGFBP)-3 binding to RXRα results in apoptosis of cancer cells [62] . DHA induces apoptosis of colonocytes [63] in an RXRα-dependent manner, while it promotes the survival of rat retina photoreceptors through RXRα-dependent activation of the mitogen-activated protein kinase (MAPK) signaling pathway [64] . Targretin suppresses the progression of colonic adenomas to adenocarcinomas in animals, which is accompanied by the induction of apoptosis [65] , while R-etodolac binds to RXRα and induces RXRα-dependent apoptosis of prostate cancer cells in vitro and in animals [66] .…”

Section: Nongenomic Activity Of Rxr and Apoptosismentioning

confidence: 99%

Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites

Zhang

Chen

et al. 2014

Acta Pharmacol Sin

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Retinoid X receptor-α (RXRα), a unique member of the nuclear receptor superfamily, represents an intriguing and unusual target for pharmacologic interventions and therapeutic applications in cancer, metabolic disorders and neurodegenerative diseases. Despite the fact that the RXR-based drug Targretin (bexarotene) is currently used for treating human cutaneous T-cell lymphoma and the fact that RXRα ligands (rexinoids) show beneficial effects in the treatment of cancer and diseases, the therapeutic potential of RXRα remains unexplored. In addition to its conventional transcription regulation activity in the nucleus, RXRα can act in the cytoplasm to modulate important biological processes, such as mitochondria-dependent apoptosis, inflammation, and phosphatidylinositol 3-kinase (PI3K)/ AKT-mediated cell survival. Recently, new small-molecule-binding sites on the surface of RXRα have been identified, which mediate the regulation of the nongenomic actions of RXRα by a class of small molecules derived from the nonsteroidal anti-inflammatory drug (NSAID) Sulindac. This review discusses the emerging roles of the nongenomic actions of RXRα in the RXRα signaling network, and their possible implications in cancer, metabolic and neurodegenerative disorders, as well as our current understanding of RXRα regulation by targeting alternate binding sites on its surface.

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Section: Nongenomic Activity Of Rxr and Apoptosismentioning

confidence: 99%

Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites

Zhang

Chen

et al. 2014

Acta Pharmacol Sin

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“…However, it has to be stressed that DHA does not produce its effects only on above mentioned pathways: it is known that DHA affects the characteristics instead of the cellular membrane [59], retinoid X receptors [60], and the dopamine transporter (DAT) activity of the cellular membrane [61]. It was shown that PUFA produces its effects by decreasing the transformation of MPTP to MPP + and monoamine oxidase-B (MAO-B) activity [62].…”

Section: Discussionmentioning

confidence: 99%

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Parlak

Özkan

Dilmaç

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on Parkinson's disease (PD). The aim of this study was to investigate if the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal nitric oxide synthase (nNOS) in an experimental mouse model of PD. Material and methods. An experimental model of PD was created by intraperitoneal injections (4 × 20 mg/kg) of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Three-month-old male C57BL/6 mice were randomly divided into four groups as follows: control (C), DHA-treated (DHA), MPTP-injected (MPTP) and DHA-treated and MPTP-injected (DHA + MPTP). DHA (36 mg/kg/day) was administered daily by gavage for four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3 activity, nitrate/nitrite and 4-hydroxynonenal (4-HNE) levels were determined by spectrophotometric assays. Immunohistochemistry was used to localize and assess the expressions of tyrosine hydroxylase (TH), nNOS and phospho-nNOS (p-nNOS) in SN.Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHA treatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities were decreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibited shorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantly decreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergic neurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreased nNOS and increased p-nNOS immunoreactivities in the DHA + MPTP group compared to the MPTP group. Conclusions. These results indicate that DHA treatment protects dopaminergic neurons in SN via increasing nNOS serine 852 phosphorylation in the experimental mice model of PD.

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“…Energy deficiencies, unmetabolized intermediates (Bakermans et al 2011), and/or a DHA deficiency (Harding et al 1999) may have a negative impact on the developing brain. DHA (22:6n-3), the most abundant omega-3 fatty acid in membrane phospholipids in the retina and in the cerebral gray matter (Fliesler and Anderson 1983;Carver et al 2001;Svennerholm 1968), is involved in neurogenesis, memory formation, and neuronal signaling and plays a major role in visual development (De Urquiza et al 2000;German et al 2013). In developing animal brains, decreased DHA levels causes deficits in neurogenesis, neurotransmitter metabolism, and altered learning and visual function although the relationships in humans are still not clear (Heaton et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency

et al. 2015

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

Cited by 40 publications

References 63 publications

Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites

Regulation of the nongenomic actions of retinoid X receptor-α by targeting the coregulator-binding sites

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency

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