Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Results
2.1. The Stress Response and Disturbances in Central Energy Metabolism Are Hallmarks of COVID-19 and IBD
2.2. Tryptophan Metabolism via Kynurenine Pathway Is Altered in Immune Triggered Disease
2.3. Hijacking of Nuclear Transcription Factors Alters the Immune Landscape
2.4. Targeting Markers Predictive of Persistent Disease in Early Immune Triggered Contexts
3. Discussion
4. Materials and Methods
4.1. Participants, Samples, and Data
4.2. Sample Preparation
4.3. Proteomic Mass Spectrometry of Biopsy, Serums, and Swab Samples
4.4. Statistical Analysis
4.5. Quantification of Kynurenine Pathway, NAD+Ome Metabolites
4.6. Racemic Amino Acid Analysis
4.7. GC Assay of Picolinic (PA) and Quinolinic (QA) Acid in NE Extracts
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Richardson, S.; Hirsch, J.S.; Narasimhan, M.; Crawford, J.M.; McGinn, T.; Davidson, K.W.; the Northwell COVID-19 Research Consortium; Barnaby, D.P.; Becker, L.B.; Chelico, J.D.; et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020, 323, 2052–2059. [Google Scholar] [CrossRef]
- Dennis, A.; Wamil, M.; Alberts, J.; Oben, J.; Cuthbertson, D.J.; Wootton, D.; Crooks, M.; Gabbay, M.; Brady, M.; Hishmeh, L.; et al. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: A prospective, community-based study. BMJ Open 2021, 11, e048391. [Google Scholar] [CrossRef] [PubMed]
- Consiglio, C.; Brodin, P. Stressful Beginnings with Long-Term Consequences. Cell 2020, 180, 820–821. [Google Scholar] [CrossRef]
- Alfei, F.; Kanev, K.; Hofmann, M.; Wu, M.; Ghoneim, H.E.; Roelli, P.; Utzschneider, D.T.; von Hoesslin, M.; Cullen, J.G.; Fan, Y.; et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 2019, 571, 265–269. [Google Scholar] [CrossRef] [PubMed]
- Liu, B.; Jayasundara, D.; Pye, V.; Dobbins, T.; Dore, G.J.; Matthews, G.; Kaldor, J.; Spokes, P. Whole of population-based cohort study of recovery time from COVID-19 in New South Wales Australia. Lancet Reg. Health-West. Pac. 2021, 12, 100193. [Google Scholar] [CrossRef] [PubMed]
- Brodin, P. Immune determinants of COVID-19 disease presentation and severity. Nat. Med. 2021, 27, 28–33. [Google Scholar] [CrossRef]
- Wang, F.; Zheng, S.; Zheng, C.; Sun, X. Attaching clinical significance to COVID-19-associated diarrhea. Life Sci. 2020, 260, 118312. [Google Scholar] [CrossRef]
- Strid, H. Prevalence of IBS-type symptoms in IBD. Lancet Gastroenterol. Hepatol. 2020, 12, 1029–1031. [Google Scholar] [CrossRef]
- Ghimire, S.; Sharma, S.; Patel, A.; Budhathoki, R.; Chakinala, R.; Khan, H.; Lincoln, M.; Georgeston, M. Diarrhea Is Associated with Increased Severity of Disease in COVID-19: Systemic Review and Metaanalysis. SN Compr. Clin. Med. 2021, 3, 28–35. [Google Scholar] [CrossRef]
- Weidinger, C.; Hegazy, A.N.; Glauben, R.; Siegmund, B. COVID-19-from mucosal immunology to IBD patients. Mucosal Immunol. 2021, 14, 566–573. [Google Scholar] [CrossRef]
- Pataskar, A.; Champagne, J.; Nagel, R.; Kenski, J.; Laos, M.; Michaux, J.; Pak, H.S.; Bleijerveld, O.B.; Mordente, K.; Navarro, J.M.; et al. Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. Nature 2022, 603, 721–727. [Google Scholar] [CrossRef] [PubMed]
- Kamel, W.; Noerenberg, M.; Cerikan, B.; Chen, H.; Järvelin, A.I.; Kammoun, M.; Lee, J.Y.; Shuai, N.; Garcia-Moreno, M.; Andrejeva, A.; et al. Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol. Cell. 2021, 81, 2851–2867. [Google Scholar] [CrossRef]
- Krämer, A.G.J.; Pollard, J., Jr. Tugendreich S Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics 2014, 30, 523–530. [Google Scholar] [CrossRef]
- Audrito, V.; Messana, V.G.; Brandimarte, L.; Deaglio, S. The Extracellular NADome Modulates Immune Responses. Front. Immunol. 2021, 121, 704779. [Google Scholar] [CrossRef] [PubMed]
- Heer, C.; Sanderson, D.J.; Voth, L.S.; Alhammad, Y.M.O.; Schmidt, M.S.; Trammell, S.A.J.; Perlman, S.; Cohen, M.S.; Fehr, A.R.; Brenner, C. Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. J. Biol. Chem. 2020, 295, 17986–17996. [Google Scholar] [CrossRef] [PubMed]
- Wasinger, V.C.; Lu, K.; Yau, Y.Y.; Nash, J.; Lee, J.; Chang, J.; Paramsothy, S.; Kaakoush, N.O.; Mitchell, H.M.; Leong, R.W. Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for ‘leaky-gut’ in inflammatory bowel disease. Sci. Rep. 2020, 10, 12932. [Google Scholar] [CrossRef] [PubMed]
- Hyland, N.; Cavanaugh, C.R.; Hornby, P.J. Emerging effects of tryptophan pathway metabolites and intestinal microbiota on metabolism and intestinal function. Amino Acids 2022, 54, 57–70. [Google Scholar] [CrossRef] [PubMed]
- Ahn, Y.; Park, S.; Choi, J.J.; Park, B.K.; Rhee, K.H.; Kang, E.; Ahn, S.; Lee, C.H.; Lee, J.S.; Inn, K.S.; et al. Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection. Nat. Microbiol. 2016, 2, 17015. [Google Scholar] [CrossRef] [Green Version]
- Munn, D.H.; Shafizadeh, E.; Attwood, J.T.; Bondarev, I.; Pashine, A.; Mellor, A.L. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 1999, 189, 1363–1372. [Google Scholar] [CrossRef]
- Patel, H.; Ashton, N.J.; Dobson, R.J.B.; Andersson, L.M.; Yilmaz, A.; Blennow, K.; Gisslen, M.; Zetterberg, H. Proteomic blood profiling in mild, severe and critical COVID-19 patients. Sci. Rep. 2021, 11, 6357. [Google Scholar] [CrossRef]
- Wiech, M.; Chroscicki, P.; Swatler, J.; Stepnik, D.; De Biasi, S.; Hampel, M.; Brewinska-Olchowik, M.; Maliszewska, A.; Sklinda, K.; Durlik, M.; et al. Remodeling of T Cell Dynamics During Long COVID is Dependent on Severity of SARS-CoV-2 Infection. Front. Immunol. 2022, 13, 886431. [Google Scholar] [CrossRef] [PubMed]
- Danlos, F.; Grajeda-Iglesias, C.; Durand, S.; Sauvat, A.; Roumier, M.; Cantin, D.; Colomba, E.; Rohmer, J.; Pommeret, F.; Baciarello, G.; et al. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers. Cell Death Dis. 2021, 12, 258. [Google Scholar] [CrossRef]
- Reyes-Ocampo, J.; Huitrón, R.L.; González-Esquivel, D.; Ugalde-Muñiz, P.; Jiménez-Anguiano, A.; Pineda, B.; Pedraza-Chaverri, J.; Ríos, C.; Pérez de la Cruz, V. Kynurenines with Neuroactive and Redox Properties: Relevance to Aging and Brain Diseases. Oxid. Med. Cell. Longev. 2014, 2014, 646909. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Molla, G.; Sacchi, S.; Bernasconi, M.; Pilone, M.S.; Fukui, K.; Polegioni, L. Characterization of human D-amino acid oxidase. FEBS Lett. 2006, 580, 2358–2364. [Google Scholar] [CrossRef] [Green Version]
- Farrow Pesci, E.C., Jr. Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal. J. Bacteriol. 2007, 189, 3425–3433. [Google Scholar] [CrossRef] [Green Version]
- Yau, Y.; Leong, R.W.; Shin, S.; Bustamante, S.; Pickford, R.; Hejazi, L.; Campbell, B.; Wasinger, V.C. Bimodal plasma metabolomics strategy identifies novel inflammatory metabolites in inflammatory bowel diseases. Discov. Med. 2014, 18, 113–124. [Google Scholar]
- Lucette, A.; Jakabek, C.D.; Bracken, S.G.; Allen-Davidian, Y.; Heng, B.; Chow, S.; Dehhaghi, M.; Pires, A.S.; Darley, D.R.; Byrne, A.; et al. Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: A longitudinal observational study. medRxiv 2022. [Google Scholar] [CrossRef]
- Voils, S.; Shoulders, B.R.; Singh, S.; Solberg, L.M.; Garrett, T.J.; Frye, R.F. Intensive Care Unit Delirium in Surgical Patients Is Associated with Upregulation in Tryptophan Metabolism. Pharmacotherapy 2020, 40, 500–506. [Google Scholar] [CrossRef] [PubMed]
- Bergström, U.; Franzén, A.; Eriksson, C.; Lindh, C.; Brittebo, E.B. Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways. J. Drug Target. 2002, 10, 469–478. [Google Scholar] [CrossRef] [PubMed]
- Mekhaeil, M.; Dev, K.K.; Conroy, M.J. Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases. Cancers 2022, 14, 687. [Google Scholar] [CrossRef]
- Badawy, A. Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: Starting with nicotinamide. Biosci. Rep. 2020, 40, BSR20202856. [Google Scholar] [CrossRef] [PubMed]
- Guedes, A.; Dileepan, M.; Jude, J.A.; Deshpande, D.A.; Walseth, T.F.; Kannan, M.S. Role of CD38/cADPR signaling in obstructive pulmonary diseases. Curr. Opin. Pharmacol. 2020, 51, 29–33. [Google Scholar] [CrossRef] [PubMed]
- Caron, E. Rac signalling: A radical view. Nat. Cell Biol. 2003, 5, 185–187. [Google Scholar] [CrossRef]
- Yue, T.; Sun, F.; Yang, C.; Wang, F.; Luo, J.; Yang, P.; Xiong, F.; Zhang, S.; Yu, Q.; Wang, C.Y. The AHR Signaling Attenuates Autoimmune Responses During the Development of Type 1 Diabetes. Front. Immunol. 2020, 11, 1510. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, L.; Hsu, E.L.; Chowdhury, G.; Dostalek, M.; Guengerich, F.P.; Bradfield, C.A. D-amino acid oxidase generates agonists of the aryl hydrocarbon receptor from D-tryptophan. Chem. Res. Toxicol. 2009, 22, 1897–1904. [Google Scholar] [CrossRef] [Green Version]
- Roager, H.; Licht, T.R. Microbial tryptophan catabolites in health and disease. Nat. Comm. 2018, 9, 3294. [Google Scholar] [CrossRef] [Green Version]
- Mackowiak, B.; Hodge, J.; Stern, S.; Wang, H. The Roles of Xenobiotic Receptors: Beyond Chemical Disposition. Drug Metab. Dispos. 2018, 46, 1361–1371. [Google Scholar] [CrossRef] [Green Version]
- Ke, X.; You, K.; Pichaud, M.; Haiser, H.; Graham, D.B.; Vlamakis, H.; Porter, J.A.; Ramnik, X.J. Gut bacterial metabolites modulate endoplasmic reticulum stress. Genome Biol. 2021, 22, 292. [Google Scholar] [CrossRef]
- Walsh, D.; Mohr, I. Viral subversion of the host protein synthesis machinery. Nat. Rev. Microbiol. 2011, 9, 860–875. [Google Scholar] [CrossRef]
- Sim, W.; Wagner, J.; Cameron, D.J.; Catto-Smith, A.G.; Bishop, R.F.; Kirkwood, C.D. Expression profile of genes involved in pathogenesis of pediatric Crohn’s disease. J. Gastroenterol. Hepatol. 2012, 276, 1083–1093. [Google Scholar] [CrossRef]
- Mun, D.G.; Vanderboom, P.M.; Madugundu, A.K.; Garapati, K.; Chavan, S.; Peterson, J.A.; Saraswat, M.; Pandey, A. DIA-Based Proteome Profiling of Nasopharyngeal Swabs from COVID-19 Patients. J. Proteome Res. 2021, 20, 4165–4175. [Google Scholar] [CrossRef] [PubMed]
- Pasternak, B.; D’Mello, S.; Jurickova, I.I.; Han, X.; Willson, T.; Flick, L.; Petiniot, L.; Uozumi, N.; Divanovic, S.; Traurnicht, A.; et al. Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn’s disease and murine colitis. Inflamm. Bowel Dis. 2010, 16, 856–869. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Perez, L. Acute phase protein response to viral infection and vaccination. Arch. Biochem. Biophys. 2019, 671, 196–202. [Google Scholar] [CrossRef]
- Petruk, G.; Puthia, M.; Petrlova, J.; Samsudin, F.; Strömdahl, A.C.; Cerps, S.; Uller, L.; Kjellström, S.; Bond, P.J.; Schmidtchen, A.A. SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity. J. Mol. Cell Biol. 2020, 12, 916–932. [Google Scholar] [CrossRef] [PubMed]
- Giron, L.; Dweep, H.; Yin, X.; Wang, H.; Damra, M.; Goldman, A.R.; Gorman, N.; Palmer, C.S.; Tang, H.Y.; Shaikh, M.W.; et al. Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients. Front. Immunol. 2021, 9, 686240. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Zhao, Y.; Feng, X.; Xu, H. SARS-CoV-2 infection threatening intestinal health: A review of potential mechanisms and treatment strategies. Crit. Rev. Food Sci. Nutr. 2022, 1–19. [Google Scholar] [CrossRef] [PubMed]
- Hoel, H.; Heggelund, L.; Reikvam, D.H.; Stiksrud, B.; Ueland, T.; Michelsen, A.E.; Otterdal, K.; Muller, K.E.; Lind, A.; Muller, F.; et al. Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement. J. Intern. Med. 2021, 289, 523–531. [Google Scholar] [CrossRef]
- Kumar, A.; Faiq, M.A.; Pareek, V.; Raza, K.; Narayan, R.K.; Prasoon, P.; Kumar, P.; Kulandhasamy, M.; Kumari, C.; Kant, K.; et al. Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients. Med. Hypotheses 2020, 144, 110271. [Google Scholar] [CrossRef]
- Braga, V. Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton. Curr. Opin. Cell Biol. 2016, 42, 138–145. [Google Scholar] [CrossRef] [Green Version]
- Ivanov, A.; Parkos, C.A.; Nusrat, A. Cytoskeletal regulation of epithelial barrier function during inflammation. Am. J. Pathol. 2010, 177, 512–524. [Google Scholar] [CrossRef]
- Wen, Z.; Zhang, Y.; Lin, Z.; Shi, K.; Jiu, Y. Cytoskeleton-a crucial key in host cell for coronavirus infection. J. Mol. Cell Biol. 2020, 12, 968–979. [Google Scholar] [CrossRef]
- Shetty, S.; van Beek, J.; Bijvank, E.; Groot, J.; Kuiling, S.; Bosch, T.; van Baarle, D.; Fuentes, S. Associations and recovery dynamics of the nasopharyngeal microbiota during influenza-like illness in the aging population. Sci. Rep. 2022, 12, 1915. [Google Scholar] [CrossRef]
- Lehtinen, M.; Hibberd, A.A.; Männikkö, S.; Yeung, N.; Kauko, T.; Forssten, S.; Lehtoranta, L.; Lahtinen, S.J.; Stahl, B.; Lyra, A.; et al. Nasal microbiota clusters associate with inflammatory response, viral load, and symptom severity in experimental rhinovirus challenge. Sci. Rep. 2018, 8, 11411. [Google Scholar] [CrossRef] [Green Version]
- Ahn, Y.; Oh, S.C.; Zhou, S.; Kim, T.D. Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target. Int. J. Mol. Sci. 2021, 22, 4523. [Google Scholar] [CrossRef] [PubMed]
- Irukayama-Tomobe, Y.; Tanaka, H.; Yokomizo, T.; Hashidate-Yoshida, T.; Yanagisawa, M.; Sakurai, T. Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc. Natl. Acad. Sci. USA 2009, 106, 3930–3934. [Google Scholar] [CrossRef] [Green Version]
- Partida-Sánchez, S.; Cockayne, D.A.; Monard, S.; Jacobson, E.L.; Oppenheimer, N.; Garvy, B.; Kusser, K.; Goodrich, S.; Howard, M.; Harmsen, A.; et al. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat. Med. 2001, 7, 1209–1216. [Google Scholar] [CrossRef] [PubMed]
- Kapolka, N.; Taghon, G.J.; Rowe, J.B.; Morgan, W.M.; Enten, J.F.; Lambert, N.A.; Isom, D.G. DCyFIR: A high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery. Proc. Natl. Acad. Sci. USA 2020, 117, 13117–13126. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, H.; Fang, J.; Maeda, H. Protective role of D-amino acid oxidase against Staphylococcus aureus infection. Infect. Immun. 2012, 80, 1546–1553. [Google Scholar] [CrossRef] [Green Version]
- Giovannoni, F.; Quintana, F.J. SARS-CoV-2-induced lung pathology: AHR as a candidate therapeutic target. Cell Res. 2021, 31, 1–2. [Google Scholar] [CrossRef]
- Sofia, M.; Ciorba, M.A.; Meckel, K.; Lim, C.K.; Guillemin, G.J.; Weber, C.R.; Bissonnette, M.; Pekow, J.R. Tryptophan Metabolism through the Kynurenine Pathway is Associated with Endoscopic Inflammation in Ulcerative Colitis. Inflamm. Bowel Dis. 2018, 24, 1471–1480. [Google Scholar] [CrossRef]
- Huhn, M.; Juan, M.H.S.; Melcher, B.; Dreis, C.; Schmidt, K.G.; Schwiebs, A.; Collins, J.; Pfeilschifter, J.M.; Vieth, M.; Stein, J.; et al. Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease. J. Clin. Med. 2020, 9, 1360. [Google Scholar] [CrossRef] [PubMed]
- Wnorowski, A.; Wnorowska, S.; Kurzepa, J.; Parada-Turska, J. Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets. Int. J. Mol. Sci. 2021, 22, 13497. [Google Scholar] [CrossRef] [PubMed]
- Farrokhpour, M.; Rezaie, N.; Moradi, N.; Ghaffari, R.F.; Izadi, S.; Azimi, M.; Zamani, F.; Izadi, S.; Ranjbar, M.; Jamshidi Makiani, M.; et al. Infliximab and Intravenous Gammaglobulin in Hospitalized Severe COVID-19 Patients in Intensive Care Unit. Arch. Iran. Med. 2021, 24, 139–143. [Google Scholar] [CrossRef]
- Harden, J.; Lewis, S.M.; Lish, S.R.; Suárez-Fariñas, M.; Gareau, D.; Lentini, T.; Johnson-Huang, L.M.; Krueger, J.G.; Lowes, M.A. The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases. J. Allergy Clin. Immunol. 2016, 137, 1830–1840. [Google Scholar] [CrossRef] [Green Version]
- Lin, Z.; Hsieh, P.W.; Hwang, T.L.; Chen, C.Y.; Sung, C.T.; Fang, J.Y. Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte-derived chemokine expression and neutrophil infiltration. FASEB J. 2018, 32, 6783–6795. [Google Scholar] [CrossRef] [Green Version]
- Thies, R.; Autor, A.P. Reactive oxygen injury to cultured pulmonary artery endothelial cells: Mediation by poly(ADP-ribose) polymerase activation causing NAD depletion and altered energy balance. Arch. Biochem. Biophys. 1991, 286, 353–363. [Google Scholar] [CrossRef]
- Wasinger, V.C.; Bustamante, S.; Boys, V.; Yau, Y.; Paramsothy, S.; Pudipeddi, A.; Corley, S.; Leong, R.W. RNA Seq and proteomics of Crohn’s disease Terminal Ileum of inflamed and non-inflamed tissue. Dryad, 2022; in press. [Google Scholar]
- Chang, J.; Leong, R.W.; Wasinger, V.C.; Ip, M.; Yang, M.; Phan, T.G. Impaired Intestinal Permeability Contributes to Ongoing Bowel Symptoms in Patients With Inflammatory Bowel Disease and Mucosal Healing. Gastroenterology 2017, 153, 723–731.e1. [Google Scholar] [CrossRef] [PubMed]
- Chang, J.; Ip, M.; Yang, M.; Wong, B.; Power, T.; Lin, L.; Xuan, W.; Phan, T.G.; Leong, R.W. The learning curve, interobserver, and intraobserver agreement of endoscopic confocal laser endomicroscopy in the assessment of mucosal barrier defects. Gastrointest. Endosc. 2016, 83, 785–791. [Google Scholar] [CrossRef] [PubMed]
- Bojkova, D.; Klann, K.; Koch, B.; Widera, M.; Krause, D.; Ciesek, S.; Cinatl, J.; Münch, C. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 2020, 583, 469–472. [Google Scholar] [CrossRef]
- Wasinger, V.; Curnoe, D.; Boel, C.; Machin, N.; Goh, H.M. The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome. Int. J. Mol. Sci. 2020, 21, 6422. [Google Scholar] [CrossRef] [PubMed]
- MacLean, B.; Tomazela, D.M.; Shulman, N.; Chambers, M.; Finney, G.L.; Frewen, B.; Kern, R.; Tabb, D.L.; Liebler, D.C.; MacCoss, M.J. Skyline: An open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 2010, 26, 966–968. [Google Scholar] [CrossRef] [PubMed]
- Ayon, N.J.; Sharma, A.D.; Gutheil, W.G. LC-MS/MS-Based Separation and Quantification of Marfey’s Reagent Derivatized Proteinogenic Amino Acid DL-Stereoisomers. J. Am. Soc. Mass Spectrom. 2019, 30, 448–458. [Google Scholar] [CrossRef] [PubMed]
- Smythe, G.A.; Poljak, A.; Bustamante, S.; Braga, O.; Maxwell, A.; Grant, R.; Sachdev, P. ECNI GC-MS analysis of picolinic and quinolinic acids and their amides in human plasma, CSF, and brain tissue. Adv. Exp. Med. Biol. 2003, 527, 705–7122. [Google Scholar] [PubMed]
- Bustamante, S.; Jayasena, T.; Richani, D.; Gilchrist, R.B.; Wu, L.E.; Sinclair, D.A.; Sachdev, P.S.; Braidy, N. Quantifying the cellular NAD+ metabolome using a tandem liquid chromatography mass spectrometry approach. Metabolomics 2017, 14, 15. [Google Scholar] [CrossRef] [PubMed]
Name | Sample Type | Analysis Type | Observations IBD | Observations COVID | ||||
---|---|---|---|---|---|---|---|---|
Biopsy | Serum | Nasal | T | P | M | |||
WARS # | Highest in Inf v Con (p = 0.03) Inf v Non Inflam (p = 0.03) Increased in Active disease Increased in Remission Increased in Severity | Increased in Acute v naïve Increased in Persistent disease v naïve Increased in Acute Resilient v Acute Persistent (Pre-COVID) Increased in Neg Resilient v Neg Persistent Increased in Critical v Con (p = 0.00003 [16]) Increased in Mild v Critical (p = 0.0000001 [16]) | ||||||
IDO2 | Highest in Inflamed (p = 0.024) | Lowest in Naïve Highest in Persistent v naïve Highest in Acute v naiive Higher in Resilient v Persistent | ||||||
Anthranilic Acid | Increased in IBD Increased with severity SES (p = 0.05) | Highest in Acute (3OH AA Acute v naïve p = 0.01) Highest in Critical (p = 0.0017 [22]) | ||||||
Kynureninase | Depleted in non-inflammed IBD Increased in Active IBD Increased in severity | Highest in Acute v naïve (p = 0.04) Increased in Persistent disease Depleted in Acute Persistent v Acute Resilient Increased in Critical v mild (p = 0.0004 [16]) | ||||||
Sum of all KP’s | Increased in all IBD | Depleted in naïve Increased in Acute v naïve (p = 0.000001) Increased in Persistent v naive (p = 0.005) Increased in Resilient v naïve (p = 0.0001) | ||||||
Quinolinic Acid | Increased in IBD | Depleted in naïve Increased in Acute v naïve (p = 0.0034) Increased in Persistent v naïve (p = 0.04) | ||||||
Picolinic Acid | Increased in IBD | Depleted in naïve Increased in Acute v naïve (p = 0.0012) Increased in Persistent v naïve (p = 0.004) | ||||||
ADPR | Not Done | Depleted in COVID Naïve Increased in Acute v Naïve | ||||||
cADPR | Not Done | Depleted in COVID Naïve Increased in Acute v Naïve | ||||||
NAM | Not done | Depleted in COVID Naïve Increased in Acute v Naïve Increased in Persistent v resilient Increased in Persistent v Acute | ||||||
PARP1 | Increased in IBD transcripts I, NI v C (p = 0.02) Increased in IBD I v NI (p = 0.03) Increased in Inflamed v Con (p = 0.001) Increased in Remission v Con Higher in Active v Con Higher in Remission v Active | Depleted in Persistent v naïve Increased in Resilient v Persistent Increased in Acute Resilient v Acute Persistent (Pre-COVID) Increased in Neg Resilient v Neg Persistent Depleted in Mild v Critical (p = 0.0000001 [16]) | ||||||
DAAO | Increased in Inflamed v Con (p = 0.05) Increased in IBD (p = 0.03) Increased in Inflamed v non-inflamed Increased in Active v con Increased in Remission v Control | Not done | ||||||
AHR | Increased in Inflamed (p = 0.04 transcript) Decreased free AHR Inflamed v non inflamed Increased in Active v Con Increased in Remission v con | Not done | ||||||
Tryptophan | Highest in Con, increasingly depleted in NI and Inflamed. D/L Tryp % increases from Con to NI to Inflamed | Homeostatic | ||||||
3-hydroxy fatty acids | Increased in inflamed Increased in Severity High ES | Not done | ||||||
HCAR3 | Increased in Inflamed v con (p = 0.03) Increased in Leak Increased in Active v Remission (p = 0.025) Increased in Active v Con Increased in Remission v Con | Increased in Acute v naïve Increased in Persistent v naïve Increased in Resilient v Persistent |
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Bustamante, S.; Yau, Y.; Boys, V.; Chang, J.; Paramsothy, S.; Pudipeddi, A.; Leong, R.W.; Wasinger, V.C. Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease. Int. J. Mol. Sci. 2022, 23, 14776. https://doi.org/10.3390/ijms232314776
Bustamante S, Yau Y, Boys V, Chang J, Paramsothy S, Pudipeddi A, Leong RW, Wasinger VC. Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease. International Journal of Molecular Sciences. 2022; 23(23):14776. https://doi.org/10.3390/ijms232314776
Chicago/Turabian StyleBustamante, Sonia, Yunki Yau, Victoria Boys, Jeff Chang, Sudarshan Paramsothy, Aviv Pudipeddi, Rupert W. Leong, and Valerie C. Wasinger. 2022. "Tryptophan Metabolism ‘Hub’ Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease" International Journal of Molecular Sciences 23, no. 23: 14776. https://doi.org/10.3390/ijms232314776