A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS

Arnold, Samuel; Amory, John K.; Walsh, Thomas J.; Isoherranen, Nina

doi:10.1194/jlr.d019745

Cited by 99 publications

(99 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4-Oxo-atRA is also detected in human plasma, suggesting that it may have biologic significance (Muindi et al, 1992b;Arnold et al, 2012). The potential biologic importance of 4-oxo-atRA is supported by studies that show that 4-oxo-atRA is teratogenic in mice and zebrafish with similar potency as atRA itself (Creech Kraft et al, 1989;Herrmann, 1995).…”

Section: Introductionmentioning

confidence: 63%

“…The formation of 4-oxo-atRA by a novel enzyme is noteworthy because 4-oxo-atRA is the only nonglucuronidated atRA metabolite detected in human plasma (Muindi et al, 1992a(Muindi et al, , 2008Arnold et al, 2012). 4-Oxo-atRA accounts for 10-20% of the atRA dose in vivo, both in plasma and as 4-oxo-RAglucuronide in the urine (Muindi et al, 1992a(Muindi et al, , 2008Arnold et al, 2012), making it a significant metabolite.…”

Section: Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

et al. 2014

Self Cite

View full text Add to dashboard Cite

All-trans-retinoic acid (atRA), the active metabolite of vitamin A, induces gene transcription via binding to nuclear retinoic acid receptors (RARs). The primary hydroxylated metabolites formed from atRA by CYP26A1, and the subsequent metabolite 4-oxoatRA, bind to RARs and potentially have biologic activity. Hence, CYP26A1, the main atRA hydroxylase, may function either to deplete bioactive retinoids or to form active metabolites. This study aimed to determine the role of CYP26A1 in modulating RAR activation via formation and elimination of active retinoids. After treatment of HepG2 cells with atRA, (4S)-OH-atRA, (4R)-OH-atRA, 4-oxo-atRA, and 18-OH-atRA, mRNAs of CYP26A1 and RARb were increased 300-to 3000-fold, with 4-oxo-atRA and atRA being the most potent inducers. However, .60% of the 4-OH-atRA enantiomers were converted to 4-oxo-atRA in the first 12 hours of treatment, suggesting that the activity of the 4-OH-atRA was due to 4-oxo-atRA. In human hepatocytes, atRA, 4-OH-atRA, and 4-oxo-atRA induced CYP26A1 and 4-oxo-atRA formation was observed from 4-OH-atRA. In HepG2 cells, 4-oxo-atRA formation was observed even in the absence of CYP26A1 activity and this formation was not inhibited by ketoconazole. In human liver microsomes, 4-oxo-atRA formation was supported by NAD 1 , suggesting that 4-oxo-atRA formation is mediated by a microsomal alcohol dehydrogenase. Although 4-oxo-atRA was not formed by CYP26A1, it was depleted by CYP26A1 (K m 5 63 nM and intrinsic clearance 5 90 ml/min per pmol). Similarly, CYP26A1 depleted 18-OH-atRA and the 4-OH-atRA enantiomers. These data support the role of CYP26A1 to clear bioactive retinoids, and suggest that the enzyme forming active 4-oxo-atRA may be important in modulating retinoid action.

show abstract

Section: Introductionmentioning

confidence: 63%

Section: Treatmentmentioning

confidence: 99%

Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Retinol and Retinyl Ester Analysis-Retinoid extractions and detections were carried out as described previously (16,22 Retinoic Acid Analysis from Testes-Intratesticular retinoic acid (RA) concentrations were measured by LC-MS/MS as described previously with a few modifications to the sample preparation (23). All sample processing, preparation, and extraction were conducted on ice under red light to minimize degradation of retinoic acids.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

Paik¹,

Haenisch²,

Müller³

et al. 2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…An unknown peak was observed in each sample that eluted between the at RA and 13-cis RA isomers. Based on the fact the 9-cis RA isomer elutes between the at RA and 13-cis RA isomers (35), MS/MS/MS was used to determine whether the unknown peak was a RA isomer. The fragmentation patterns of the at RA and 13-cis RA isomers were identical and generated MS/MS/MS fragments of m/z 159 ( Fig.…”

Section: Correlation Of Intratesticular Ra Concentrations With Aldh1amentioning

confidence: 99%

“…The concentrations of at RA, 13-cis RA, and retinal were measured using an AB Sciex 5500 qTrap Q-LIT mass spectrometer equipped with an Agilent 1290 UHPLC as previously described ( 35 ) with several minor modifi cations. Briefl y, at RA and 13-cis RA were monitored using positive ion APCI and MS transitions of m/z 301 → 205 and m/z 301 → 123 with the 205 fragment used for quantifi cation.…”

Section: Mass Spectrometric Quantifi Cation Of At Ra 13-cis Ra and mentioning

confidence: 99%

Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations

Arnold

Kent

Hogarth

et al. 2015

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS

Cited by 99 publications

References 34 publications

Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations

Contact Info

Product

Resources

About