New HPLC Eevidence on Endogenous Tauret in Retina and Pigment Epithelium

Petrosian, A. M.; Haroutounian, Jasmine E.; Gundersen, Thomas E.; Blomhoff, Rune; Fugelli, K.; Kanli, H.

doi:10.1007/0-306-46838-7_50

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…We have previously developed several methods for retinoid analysis22–26 and used these in several applications 14, 15, 27–30. The focus has always been directed towards preserving the labile retinoids, and, as a result, rather complex multidimensional systems have been developed.…”

Section: Resultsmentioning

confidence: 99%

Quantitative high‐throughput determination of endogenous retinoids in human plasma using triple‐stage liquid chromatography/tandem mass spectrometry

Gundersen

Bastani

Blomhoff

2007

Rapid Comm Mass Spectrometry

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A high-throughput ultrasensitive analytical method based on liquid chromatography with positive ion atmospheric pressure chemical ionization (APCI) coupled to tandem mass spectrometric detection (LC/MS/MS) was developed for the determination of all-trans-4-oxo-retinoic acid (at4oxoRA), 13-cis-4-oxo-retinoic acid (13c4oxoRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (atRA) and all-trans-retinol (atROH) in human plasma. A stable isotope of atRA was used as internal standard (IS). The analytes and IS were isolated from 100 microL plasma by acetonitrile mono-phase extraction (MPE) performed in black 96-well microtiterplates. A 100 microL injection was focused on-column and chromatographed on an Agilent ZORBAX SB-C18 rapid-resolution high-throughput (RRHT) column with 1.8-microm particles (4.6 mmx50 mm) maintained at 60 degrees C. The initial mobile phase composition was acetonitrile/water/formic acid (10:90:0.1, v/v/v) delivered at 1.8 mL/min. Elution was accomplished by a fast gradient to acetonitrile/methanol/formic acid (90:10:0.1, v/v/v). The method had a chromatographic total run time of 7 min. An Applied Biosystems 4000 Q TRAP linear tandem mass spectrometer equipped with a heated nebulizer (APCI) ionization source was operated in multiple reaction monitoring (MRM) mode with the precursor-to-product ion transitions m/z 315.4-->297 (4-oxo-retinoic acids), 301.2-->205 (retinoic acids), 305.0-->209 (IS) and 269.2-->93 (retinol) used for quantification. The assay was fully validated and found to have acceptable accuracy, precision, linearity, sensitivity and selectivity. The mean extraction recoveries from spiked plasma samples were 80-105% for the various retinoids at three different levels. The intra-day accuracy of the assay was within 8% of nominal and intra-day precision was better than 8% coefficient of variance (CV) for retinoic acids. Inter-day precision results for quality control samples run over a 12-day period alongside clinical samples showed mean precision better than 12.5% CV. The limit of quantification was in the range of 0.1-0.2 ng/mL and the mass limit of detection (mLOD) was in the range 1-4 pg on column for the retinoic acids. The assay has been successfully applied to the analysis of 1700 plasma samples.

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Section: Resultsmentioning

confidence: 99%

Quantitative high‐throughput determination of endogenous retinoids in human plasma using triple‐stage liquid chromatography/tandem mass spectrometry

Gundersen

Bastani

Blomhoff

2007

Rapid Comm Mass Spectrometry

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“…It was recognized a number of years ago that retinaldehyde also combines with the endogenous sulfur-containing amino acid taurine to produce the taurine-retinaldehyde Schiff base, A1-taurine (A1T) ( 25 ) ( Fig. 1 ).…”

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confidence: 99%

Vitamin A aldehyde-taurine adduct and the visual cycle

Kim

Sparrow

2020

Proc. Natl. Acad. Sci. U.S.A.

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Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11-cis-retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11-cis- to all-trans-retinal configuration. Continued light sensitivity necessitates the regeneration of 11-cis-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells to facilitate retinoid trafficking, to prevent nonspecific reactivity, and to conserve the 11-cis configuration. Here we show that redundancy in this system is provided by a protonated Schiff base adduct of retinaldehyde and taurine (A1-taurine, A1T) that forms reversibly by nonenzymatic reaction. A1T was present as 9-cis, 11-cis, 13-cis, and all-trans isomers, and the total levels were higher in neural retina than in retinal pigment epithelium (RPE). A1T was also more abundant under conditions in which 11-cis-retinaldehyde was higher; this included black versus albino mice, dark-adapted versus light-adapted mice, and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. Taurine levels paralleled these differences in A1T. Moreover, A1T was substantially reduced in mice deficient in the Rpe65 isomerase and in mice deficient in cellular retinaldehyde-binding protein; in these models the production of 11-cis-retinal is compromised. A1T is an amphiphilic small molecule that may represent a mechanism for escorting retinaldehyde. The transient Schiff base conjugate that the primary amine of taurine forms with retinaldehyde would readily hydrolyze to release the retinoid and thus may embody a pool of 11-cis-retinal that can be marshalled in photoreceptor cells.

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“…Bisretinoid formation in photoreceptor cells occurs due to unchecked retinaldehyde reactivity. Since taurine sequesters retinaldehyde via formation of the Schiff base A1T [ 16 , 17 ] one might have expected to find that taurine supplementation with the associated formation of A1T would reduce unwanted bisretinoid formation. Instead, we found that taurine-treatment had no effect on bisretinoid formation in young Abca4 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

“…Taurine carries a primary amine that in retina reversibly binds to retinaldehyde thereby forming a small molecule, taurine-retinaldehyde Schiff base (A1T) [ 16 , 17 ]. A1T is an amphiphilic molecule carrying a negatively charged sulfonated group together with a hydrophobic retinoid moiety and may serve to chaperone retinaldehyde, a molecule that is otherwise poorly soluble in aqueous media.…”

Section: Introductionmentioning

confidence: 99%

“…A1T is an amphiphilic molecule carrying a negatively charged sulfonated group together with a hydrophobic retinoid moiety and may serve to chaperone retinaldehyde, a molecule that is otherwise poorly soluble in aqueous media. We recently showed that A1T is present at higher levels in neural retina as opposed to RPE and is more abundant under conditions in which 11- cis -retinaldehyde is more abundant [ 16 , 17 ]. These conditions included mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant, the presence versus absence of ocular pigmentation, dark-adaptation versus light-adaptation.…”

Section: Introductionmentioning

confidence: 99%

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