Characterization of a new endogenous vitamin A metabolite

Schmidt, Carsten K.; Volland, Jutta; Hamscher, Gerd; Nau, Heinz

doi:10.1016/s1388-1981(02)00212-3

Cited by 47 publications

(36 citation statements)

References 49 publications

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“…However, 9-cis-RA detection in vertebrates is rare; in the mouse embryonic spinal cord, 9-cis-RA was detected only after atRA levels were artificially elevated and others report that 9-cis-RA levels are below their limits of detection (Schmidt et al, 2002). The relevance of a physiological role for 9-cis-RA has thus been questioned , although there is recent evidence in the vertebrate nervous system to suggest its role in reducing the production of inflammatory cytokines from activated glia (Xu and Drew, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…9-cis-RA has been difficult to detect previously, either due to its low endogenous concentration (Schmidt et al, 2002) or its potential for isomerization to atRA and/or 13-cis-RA (Kraft and Juchau, 1993;Shirley et al, 1996). We cannot rule out the possibility that the 9-cis-RA detected in our samples arose as a consequence of its isomerization from atRA during the extraction procedure.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Dmetrichuk

Carlone²,

Jones³

et al. 2008

J. Neurosci.

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Retinoic acid (RA) is an active metabolite of Vitamin A that plays an important role in the growth and differentiation of many cell types. All-trans RA (atRA) is the retinoic acid isomer that has been most widely studied in the nervous system, and can induce and direct neurite outgrowth from both vertebrate and invertebrate preparations. The presence and role of the 9-cis-RA isomer in the nervous system is far less well defined. Here, we used high-pressure liquid chromatography (HPLC) and mass spectrometry (MS) to show for the first time, the presence of both atRA and 9-cis-RA in the CNS of an invertebrate. We then demonstrated that 9-cis-RA was capable of exerting the same neurotrophic and chemotropic effects on cultured neurons as atRA. In this study, significantly more cells showed neurite outgrowth in 9-cis-RA versus the EtOH vehicle control, and 9-cis-RA significantly increased the number and length of neurites from identified neurons after 4 d in culture. 9-cis-RA also extended the duration of time that cells remained electrically excitable in culture. Furthermore, we showed for the first time in any species, that exogenous application of 9-cis-RA induced positive growth cone turning of cultured neurons. This study provides the first evidence for the presence of both atRA and 9-cis-RA in an invertebrate CNS and also provides the first direct evidence for a potential physiological role for 9-cis-RA in neuronal regeneration and axon pathfinding.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Dmetrichuk

Carlone²,

Jones³

et al. 2008

J. Neurosci.

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“…Experimental blanks were taken by extracting 2 L of ultrapure water using the same method as described above, and none of them were detected to exhibit RAR agonistic activities. The urine sample was treated using the same procedure as the water samples, and the serum sample was prepared as described in a previous study (32). Two-Step Reversed-Phase Fractionation Using HPLC and UPLC.…”

Section: Methodsmentioning

confidence: 99%

Identification of Retinoic Acid Receptor Agonists in Sewage Treatment Plants

Zhen

et al. 2009

Environ. Sci. Technol.

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Retinoic acid receptor (RAR) agonists are speculated to be one possible cause for the widely observed frog deformities in North America, although little is known about the specific RAR agonists in aquatic environments. We identified the specific RAR agonists in sewage treatment plants (STPs) and receiving rivers using an RAR yeast two-hybrid bioassay. Water samples were extracted by solid-phase extract cartridges, which were successively eluted by hexane, ethyl acetate, and methanol for bioassay. Among the three fractions, the ethyl acetate fraction showed the highest RAR agonistic activities. The bioassay-derived activity, expressed as all-trans-retinoic acid (all-trans-RA) equivalents (ATRA-EQ) were 10.9 ( 2.2 and 1.7 ( 1.0 ng/L in the STP influents and effluents, respectively, while the ATRA-EQs were as high as 7.1 and 8.3 ng/L in the two rivers receiving STP effluents. Following a two-step fractionation using high-performance liquid chromatography and ultraperformance liquid chromatography (UPLC) directed by the bioassay, two bioactive fractions were obtained from Gaobeidian STP influent and all-trans-4-oxo-RA (4.7-10.4 ng/L in influents, <0.2-0.9 ng/L in effluents) and 13-cis-4-oxo-RA (2.3-7.1 ng/L in influents, <0.4-1.1 ng/L in effluents) were identified in these fractions with UPLC-MS/MS. The EC 50 for all-trans-4-oxo-RA or 13-cis-4-oxo-RA relative to that of all-trans-RA in exhibiting RARR agonistic activity was calculated to be 3.87 and 0.46, respectively.

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“…MS/MS in the form of an iontrap mass spectrometer was recently used for the characterization of the retinoids14-hydroxy-retro-retinol and 4-hydroxyretinol in the liver of neonatal rats at days 3 and 11 after birth and the novel retinoid 9-cis-4-oxo-13,14-dihydro-RA in adult mouse liver and also human liver (Schmidt et al, 2002). Others have used normal phase LC-APCI-MS/MS (iontrap) for quantification of ROH and RA in 8-week-old rat liver and retinae from embryonic day 13-15 (McCaffery et al, 2002).…”

Section: Liquid Chromatography-mass Spectrometry (Lc-ms)mentioning

confidence: 99%

Methods for detecting and identifying retinoids in tissue

Gundersen

2006

J. Neurobiol.

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Methods for retinoid analysis in tissue include direct spectrophotometry or fluorometry and retinoid responsive reporter constructs in the form of cell reporter assays or transgenic reporter animals, but chromatographic methods dominate and posses several superior features in quantitative analysis. The multitude of extraction protocols used can coarsely be divided into manual liquid-liquid extraction protocols and semi-or fully automated solid phase extraction-based protocols.Liquid chromatographic separation in reversed phase dominates although normal phase is also used. Detection is mainly performed with UV detectors although electrochemical and fluorescence detection is also used. Mass spectrometry in combination with LC is more often used in retinoid analysis and is likely to dominate in the future.

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Characterization of a new endogenous vitamin A metabolite

Cited by 47 publications

References 49 publications

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Detection of Endogenous Retinoids in the Molluscan CNS and Characterization of the Trophic and Tropic Actions of 9-cisRetinoic Acid on Isolated Neurons

Identification of Retinoic Acid Receptor Agonists in Sewage Treatment Plants

Methods for detecting and identifying retinoids in tissue

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