Altered Tryptophan Catabolism in Placentas From Women With Pre-eclampsia

Overview

Journal Int J Tryptophan Res

Publisher Sage Publications

Specialty Biochemistry

Date 2019 Apr 23

PMID 31007529

Citations 19

Authors

Sarah A Keaton

Patrick Heilman

Elena Y Bryleva

Zachary Madaj

Stanislaw Krzyzanowski

Jamie Grit

Emily S Miller

Maya Jalmby

Grigoros Kalapotharakos

Karen Racicot

Asgerally Fazleabas

Stefan R Hansson

Lena Brundin

Affiliations

Soon will be listed here.

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.

Citing Articles

Pregnancy Metabolic Adaptation and Changes in Placental Metabolism in Preeclampsia.

Li Y, Ma L, He R, Teng F, Qin X, Liang X Geburtshilfe Frauenheilkd. 2024; 84(11):1033-1042.

PMID: 39524034 PMC: 11543110. DOI: 10.1055/a-2403-4855.

Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.

Pocivavsek A, Schwarcz R, Erhardt S Pharmacol Rev. 2024; 76(6):978-1008.

PMID: 39304346 PMC: 11549936. DOI: 10.1124/pharmrev.124.000239.

The Molecular Basis of the Augmented Cardiovascular Risk in Offspring of Mothers with Hypertensive Disorders of Pregnancy.

Svigkou A, Katsi V, Kordalis V, Tsioufis K Int J Mol Sci. 2024; 25(10).

PMID: 38791492 PMC: 11121482. DOI: 10.3390/ijms25105455.

Dysregulated placental expression of kynurenine pathway enzymes is associated with inflammation and depression in pregnancy.

Sha Q, Escobar Galvis M, Madaj Z, Keaton S, Smart L, Edgerly Y Brain Behav Immun. 2024; 119:146-153.

PMID: 38555986 PMC: 11210184. DOI: 10.1016/j.bbi.2024.03.042.

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia.

Ramirez-Armas R, Garza-Veloz I, Olivas-Chavez J, Covarrubias-Carrillo R, Martinez-Vazquez M, Monarrez-Espino J J Pers Med. 2023; 13(11).

PMID: 38003850 PMC: 10671924. DOI: 10.3390/jpm13111535.

References

Hennessy A, Pilmore H, Simmons L, Painter D . A deficiency of placental IL-10 in preeclampsia. J Immunol. 1999; 163(6):3491-5. View

Dang Y, DALE W, Brown O . Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway. Free Radic Biol Med. 2000; 28(4):615-24. DOI: 10.1016/s0891-5849(99)00272-5. View

Thomas S, Stocker R . Antioxidant activities and redox regulation of interferon-gamma-induced tryptophan metabolism in human monocytes and macrophages. Adv Exp Med Biol. 2000; 467:541-52. DOI: 10.1007/978-1-4615-4709-9_67. View

Thomas S, Stocker R . Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox Rep. 2000; 4(5):199-220. DOI: 10.1179/135100099101534927. View

Smythe G, Braga O, Brew B, Grant R, Guillemin G, Kerr S . Concurrent quantification of quinolinic, picolinic, and nicotinic acids using electron-capture negative-ion gas chromatography-mass spectrometry. Anal Biochem. 2002; 301(1):21-6. DOI: 10.1006/abio.2001.5490. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Sedlmayr P, Blaschitz A, Wintersteiger R, Semlitsch M, Hammer A, MacKenzie C . Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta. Mol Hum Reprod. 2002; 8(4):385-91. DOI: 10.1093/molehr/8.4.385. View

Brown M, Lindheimer M, de Swiet M, Van Assche A, Moutquin J . The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2002; 20(1):IX-XIV. DOI: 10.1081/PRG-100104165. View

Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A . T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002; 9(10):1069-77. DOI: 10.1038/sj.cdd.4401073. View

10.

Stone T, Darlington L . Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov. 2002; 1(8):609-20. DOI: 10.1038/nrd870. View

11.

Rein D, Breidenbach M, Honscheid B, Friebe-Hoffmann U, Engel H, Gohring U . Preeclamptic women are deficient of interleukin-10 as assessed by cytokine release of trophoblast cells in vitro. Cytokine. 2003; 23(4-5):119-25. DOI: 10.1016/s1043-4666(03)00220-5. View

12.

SENIOR J, FAHIM I, Sullivan F, Robson J . POSSIBLE ROLE OF 5-HYDROXYTRYPTAMINE IN TOXAEMIA OF PREGNANCY. Lancet. 1963; 2(7307):553-4. DOI: 10.1016/s0140-6736(63)92647-3. View

13.

Manuelpillai U, Nicholls T, Wallace E, Phillips D, Guillemin G, Walker D . Increased mRNA expression of kynurenine pathway enzymes in human placentae exposed to bacterial endotoxin. Adv Exp Med Biol. 2004; 527:85-9. DOI: 10.1007/978-1-4615-0135-0_9. View

14.

Makris A, Xu B, Yu B, Thornton C, Hennessy A . Placental deficiency of interleukin-10 (IL-10) in preeclampsia and its relationship to an IL10 promoter polymorphism. Placenta. 2005; 27(4-5):445-51. DOI: 10.1016/j.placenta.2005.05.003. View

15.

Perkins A . Endogenous anti-oxidants in pregnancy and preeclampsia. Aust N Z J Obstet Gynaecol. 2006; 46(2):77-83. DOI: 10.1111/j.1479-828X.2006.00532.x. View

16.

Jauniaux E, Poston L, Burton G . Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006; 12(6):747-55. PMC: 1876942. DOI: 10.1093/humupd/dml016. View

17.

Rafice S, Chauhan N, Efimov I, Basran J, Raven E . Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase. Biochem Soc Trans. 2009; 37(Pt 2):408-12. DOI: 10.1042/BST0370408. View

18.

Redman C . Current topic: pre-eclampsia and the placenta. Placenta. 1991; 12(4):301-8. DOI: 10.1016/0143-4004(91)90339-h. View

19.

Dinatale B, Murray I, Schroeder J, Flaveny C, Lahoti T, Laurenzana E . Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci. 2010; 115(1):89-97. PMC: 2855350. DOI: 10.1093/toxsci/kfq024. View

20.

Myatt L . Review: Reactive oxygen and nitrogen species and functional adaptation of the placenta. Placenta. 2010; 31 Suppl:S66-9. PMC: 2832707. DOI: 10.1016/j.placenta.2009.12.021. View