Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia

Sarah A. Keaton, Patrick Heilman, Elena Y. Bryleva, Zachary Madaj, Stanislaw Krzyzanowski, Jamie Grit, Emily Stinnett Miller, Maya Jälmby, Grigoros Kalapotharakos, Karen Racicot, Asgerally Fazleabas, Stefan R. Hansson, Lena Brundin*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.

Original languageEnglish (US)
JournalInternational Journal of Tryptophan Research
Volume12
DOIs
StatePublished - Apr 1 2019

Fingerprint

Kynurenine
Pre-Eclampsia
Tryptophan
Placenta
Serum Amyloid A Protein
Metabolites
Tryptophan Oxygenase
Enzymes
High pressure liquid chromatography
Tissue
Indoleamine-Pyrrole 2,3,-Dioxygenase
Quinolinic Acid
Inflammation Mediators
Oxygenases
Interleukin-1
Gas chromatography
Mass spectrometry
Interleukin-6
Gas Chromatography-Mass Spectrometry
High Pressure Liquid Chromatography

Keywords

  • indoleamine 2,3-dioxygenase
  • kynurenine pathway
  • pre-eclampsia
  • serum amyloid A
  • tryptophan
  • tryptophan 2,3-dioxygenase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Keaton, S. A., Heilman, P., Bryleva, E. Y., Madaj, Z., Krzyzanowski, S., Grit, J., ... Brundin, L. (2019). Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia. International Journal of Tryptophan Research, 12. https://doi.org/10.1177/1178646919840321
Keaton, Sarah A. ; Heilman, Patrick ; Bryleva, Elena Y. ; Madaj, Zachary ; Krzyzanowski, Stanislaw ; Grit, Jamie ; Miller, Emily Stinnett ; Jälmby, Maya ; Kalapotharakos, Grigoros ; Racicot, Karen ; Fazleabas, Asgerally ; Hansson, Stefan R. ; Brundin, Lena. / Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia. In: International Journal of Tryptophan Research. 2019 ; Vol. 12.
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title = "Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia",
abstract = "Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.",
keywords = "indoleamine 2,3-dioxygenase, kynurenine pathway, pre-eclampsia, serum amyloid A, tryptophan, tryptophan 2,3-dioxygenase",
author = "Keaton, {Sarah A.} and Patrick Heilman and Bryleva, {Elena Y.} and Zachary Madaj and Stanislaw Krzyzanowski and Jamie Grit and Miller, {Emily Stinnett} and Maya J{\"a}lmby and Grigoros Kalapotharakos and Karen Racicot and Asgerally Fazleabas and Hansson, {Stefan R.} and Lena Brundin",
year = "2019",
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Keaton, SA, Heilman, P, Bryleva, EY, Madaj, Z, Krzyzanowski, S, Grit, J, Miller, ES, Jälmby, M, Kalapotharakos, G, Racicot, K, Fazleabas, A, Hansson, SR & Brundin, L 2019, 'Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia', International Journal of Tryptophan Research, vol. 12. https://doi.org/10.1177/1178646919840321

Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia. / Keaton, Sarah A.; Heilman, Patrick; Bryleva, Elena Y.; Madaj, Zachary; Krzyzanowski, Stanislaw; Grit, Jamie; Miller, Emily Stinnett; Jälmby, Maya; Kalapotharakos, Grigoros; Racicot, Karen; Fazleabas, Asgerally; Hansson, Stefan R.; Brundin, Lena.

In: International Journal of Tryptophan Research, Vol. 12, 01.04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia

AU - Keaton, Sarah A.

AU - Heilman, Patrick

AU - Bryleva, Elena Y.

AU - Madaj, Zachary

AU - Krzyzanowski, Stanislaw

AU - Grit, Jamie

AU - Miller, Emily Stinnett

AU - Jälmby, Maya

AU - Kalapotharakos, Grigoros

AU - Racicot, Karen

AU - Fazleabas, Asgerally

AU - Hansson, Stefan R.

AU - Brundin, Lena

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.

AB - Background: The kynurenine pathway enzymes, breaking down tryptophan, are abundant in placental tissue. These metabolites are involved in immunoregulatory mechanisms, although the role of this pathway in pre-eclampsia (PE) has only begun to be characterized. Here, we determined tryptophan and metabolite levels together with the expression of kynurenine pathway enzymes and inflammatory factors in placental tissue from women with and without PE. Methods: Thirty-six placentas (18 PE and 18 controls) were analyzed for expression of kynurenine pathway enzymes indoleamine-2,3-dioxygenase (IDO1 and 2), tryptophan-2,3-dioxygenase (TDO), kynurenine-3-mono-oxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) as well as interleukin (IL)-1β, IL-6, and serum amyloid A (SAA). Tryptophan and kynurenine content were measured using high-pressure liquid chromatography and quinolinic acid was measured using gas chromatography-mass spectrometry. Conclusions: Tryptophan content was reduced in placentas from women with PE. There was an increased kynurenine/tryptophan ratio in placentas from women with PE but no significant change in downstream metabolites. We confirmed a reduction in IDO1 expression and found a compensatory increase in TDO expression in placentas from women with PE. SAA was reduced in PE placentas compared with controls. Our data show that tryptophan content and the inflammatory mediator SAA are both compromised in placentas from women with PE. Further studies on the role of tryptophan catabolism and mediators of inflammation in sustaining healthy immunobiological pathways in the placenta are warranted.

KW - indoleamine 2,3-dioxygenase

KW - kynurenine pathway

KW - pre-eclampsia

KW - serum amyloid A

KW - tryptophan

KW - tryptophan 2,3-dioxygenase

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