Glutathione peroxidase 3 is a potential biomarker for konzo.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 Sep 2024
06 Sep 2024
Historique:
received:
08
02
2024
accepted:
27
08
2024
medline:
7
9
2024
pubmed:
7
9
2024
entrez:
6
9
2024
Statut:
epublish
Résumé
Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world's poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.
Identifiants
pubmed: 39242582
doi: 10.1038/s41467-024-52136-5
pii: 10.1038/s41467-024-52136-5
doi:
Substances chimiques
Biomarkers
0
Glutathione Peroxidase
EC 1.11.1.9
GPX3 protein, human
EC 1.11.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7811Subventions
Organisme : U.S. Department of Health & Human Services | NIH | Fogarty International Center (FIC)
ID : 5K01TW011772-03
Organisme : U.S. Department of Health & Human Services | NIH | Fogarty International Center (FIC)
ID : 5R01ES019841-10
Informations de copyright
© 2024. The Author(s).
Références
Kashala-Abotnes, E. et al. Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning. Brain Res. Bull. 145, 87–91 (2019).
pubmed: 29981837
doi: 10.1016/j.brainresbull.2018.07.001
Mwanza, J. C., Tshala-Katumbay, D. & Tylleskär, T. Neuro-ophthalmologic manifestations of konzo. Environ. Toxicol. Pharm. 19, 491–496 (2005).
doi: 10.1016/j.etap.2004.12.012
Boivin, M. J. et al. Neuropsychological effects of konzo: a neuromotor disease associated with poorly processed cassava. Pediatrics 131, e1231–e1239 (2013).
pubmed: 23530166
pmcid: 3608487
doi: 10.1542/peds.2012-3011
Tylleskär, T. et al. Epidemiological evidence from Zaire for a dietary etiology of konzo, an upper motor neuron disease. Bull. World Health Organ. 69, 581–589 (1991).
pubmed: 1959159
pmcid: 2393256
Cliff, J. et al. Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem. Toxicol. 49, 631–635 (2011).
pubmed: 20654676
doi: 10.1016/j.fct.2010.06.056
Bramble, M. S. et al. The gut microbiome in konzo. Nat. Commun. 12, 5371 (2021).
pubmed: 34508085
pmcid: 8433213
doi: 10.1038/s41467-021-25694-1
Oluwole, O. S. Cyclical konzo epidemics and climate variability. Ann. Neurol. 77, 371–380 (2015).
pubmed: 25523348
doi: 10.1002/ana.24334
Hendry-Hofer, T. B. et al. A Review on Ingested Cyanide: Risks, Clinical Presentation, Diagnostics, and Treatment Challenges. J. Med Toxicol. 15, 128–133 (2019).
pubmed: 30539383
doi: 10.1007/s13181-018-0688-y
Swenne, I. et al. Cyanide detoxification in rats exposed to acetonitrile and fed a low protein diet. Fundam. Appl Toxicol. 32, 66–71 (1996).
pubmed: 8812227
doi: 10.1006/faat.1996.0107
Baguma, M. et al. Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review. Neurotoxicology 85, 54–67 (2021).
pubmed: 33964344
doi: 10.1016/j.neuro.2021.05.001
Cliff, J. et al. Association of high cyanide and low sulphur intake in cassava-induced spastic paraparesis. Lancet 2, 1211–1213 (1985).
pubmed: 2866292
doi: 10.1016/S0140-6736(85)90742-1
Nzwalo, H. & Cliff, J. Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease. PLoS Negl. Trop. Dis. 5, e1051 (2011).
pubmed: 21738800
pmcid: 3125150
doi: 10.1371/journal.pntd.0001051
Nunn, P. B., Lyddiard, J. R. & Christopher Perera, K. P. Brain glutathione as a target for aetiological factors in neurolathyrism and konzo. Food Chem. Toxicol. 49, 662–667 (2011).
pubmed: 20816718
doi: 10.1016/j.fct.2010.08.037
Dias, V., Junn, E. & Mouradian, M. M. The role of oxidative stress in Parkinson’s disease. J. Parkinsons Dis. 3, 461–491 (2013).
pubmed: 24252804
pmcid: 4135313
doi: 10.3233/JPD-130230
Kumar, A. & Ratan, R. R. Oxidative Stress and Huntington’s Disease: The Good, The Bad, and The Ugly. J. Huntingt. Dis. 5, 217–237 (2016).
doi: 10.3233/JHD-160205
Huang, W. J., Zhang, X. & Chen, W. W. Role of oxidative stress in Alzheimer’s disease. Biomed. Rep. 4, 519–522 (2016).
pubmed: 27123241
pmcid: 4840676
doi: 10.3892/br.2016.630
Hemerková, P. & Vališ, M. Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies. Biomolecules 11, 437 (2021).
Bumoko, G. M. et al. Lower serum levels of selenium, copper, and zinc are related to neuromotor impairments in children with konzo. J. Neurol. Sci. 349, 149–153 (2015).
pubmed: 25592410
pmcid: 4323625
doi: 10.1016/j.jns.2015.01.007
Makila-Mabe, B. G. et al. Serum 8,12-iso-iPF2α-VI isoprostane marker of oxidative damage and cognition deficits in children with konzo. PLoS One 9, e107191 (2014).
pubmed: 25222616
pmcid: 4164531
doi: 10.1371/journal.pone.0107191
Tanaka, H. et al. ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis. J. Neurol. 260, 1782–1797 (2013).
pubmed: 23436019
doi: 10.1007/s00415-013-6877-3
Restuadi, R. et al. Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1. Genome Med 14, 7 (2022).
pubmed: 35042540
pmcid: 8767698
doi: 10.1186/s13073-021-01006-6
Chang, C. et al. Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer. Cancers, 12, 2197 (2020).
Trolli, G., Résumé des observations réunies, au Kwango, au sujet de deux affections d’origine indéterminée. (1938).
Banea, M. et al. [High prevalence of konzo associated with a food shortage crisis in the Bandundu region of zaire]. Ann. Soc. Belg. Med Trop. 72, 295–309 (1992).
pubmed: 1292426
Tshala-Katumbay, D. et al. Cassava food toxins, konzo disease, and neurodegeneration in sub-Sahara Africans. Neurology 80, 949–951 (2013).
pubmed: 23460617
pmcid: 3653209
doi: 10.1212/WNL.0b013e3182840b81
Tshala Katumbay, D., Lukusa, V. M. & Eeg-Olofsson, K. E. EEG findings in Konzo: a spastic para/tetraparesis of acute onset. Clin. Electroencephalogr. 31, 196–200 (2000).
pubmed: 11056842
doi: 10.1177/155005940003100408
Tshala-Katumbay, D. et al. Analysis of motor pathway involvement in konzo using transcranial electrical and magnetic stimulation. Muscle Nerve 25, 230–235 (2002).
pubmed: 11870691
doi: 10.1002/mus.10029
Tylleskär, T. et al. Konzo: a distinct disease entity with selective upper motor neuron damage. J. Neurol. Neurosurg. Psychiatry 56, 638–643 (1993).
pubmed: 8509777
pmcid: 489613
doi: 10.1136/jnnp.56.6.638
Rwatambuga, F. A. et al. Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives. Food Chem. Toxicol. 148, 111917 (2021).
pubmed: 33296712
doi: 10.1016/j.fct.2020.111917
Brigelius-Flohé, R. & Maiorino, M. Glutathione peroxidases. Biochim Biophys. Acta 1830, 3289–3303 (2013).
pubmed: 23201771
doi: 10.1016/j.bbagen.2012.11.020
Nirgude, S. & Choudhary, B. Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer. Biochem Pharm. 184, 114365 (2021).
pubmed: 33310051
doi: 10.1016/j.bcp.2020.114365
Moghadaszadeh, B. & Beggs, A. H. Selenoproteins and their impact on human health through diverse physiological pathways. Physiology 21, 307–315 (2006).
pubmed: 16990451
doi: 10.1152/physiol.00021.2006
Hill, K. E. et al. Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects. J. Nutr. 126, 138–145 (1996).
pubmed: 8558294
doi: 10.1093/jn/126.1.138
Huang, W. et al. Selenoprotein P and glutathione peroxidase (EC 1.11.1.9) in plasma as indices of selenium status in relation to the intake of fish. Br. J. Nutr. 73, 455–461 (1995).
pubmed: 7766568
doi: 10.1079/BJN19950047
Lopes, S. O. et al. Food Insecurity and Micronutrient Deficiency in Adults: A Systematic Review and Meta-Analysis. Nutrients, 15, 1074 (2023).
Haug, A. et al. How to use the world’s scarce selenium resources efficiently to increase the selenium concentration in food. Micro. Ecol. Health Dis. 19, 209–228 (2007).
Singh, A. et al. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24, 1583 (2019).
Benyamin, B. et al. Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis. Nat. Commun. 8, 611 (2017).
pubmed: 28931804
pmcid: 5606989
doi: 10.1038/s41467-017-00471-1
Wang, J. Y. et al. Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer. Clin. Chim. Acta 411, 1432–1436 (2010).
pubmed: 20576521
doi: 10.1016/j.cca.2010.05.026
Liu, C. et al. Effects of GSTA1 and GPX3 Polymorphisms on the Risk of Schizophrenia in Chinese Han Population. Neuropsychiatr. Dis. Treat. 16, 113–118 (2020).
pubmed: 32021204
pmcid: 6957098
doi: 10.2147/NDT.S236298
Grond-Ginsbach, C. et al. GPx-3 gene promoter variation and the risk of arterial ischemic stroke. Stroke 38, e23 (2007). author reply e24.
pubmed: 17463310
doi: 10.1161/STROKEAHA.106.479444
Tshala-Katumbay, D. et al. Impairments, disabilities and handicap pattern in konzo–a non-progressive spastic para/tetraparesis of acute onset. Disabil. Rehabil. 23, 731–736 (2001).
pubmed: 11732562
doi: 10.1080/09638280110055075
Salim, S. Oxidative Stress and the Central Nervous System. J. Pharm. Exp. Ther. 360, 201–205 (2017).
doi: 10.1124/jpet.116.237503
Seeber, B. E. et al. The vitamin E-binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis. Fertil. Steril. 94, 2923–2926 (2010).
pubmed: 20858448
pmcid: 2996608
doi: 10.1016/j.fertnstert.2010.05.008
Jo, M. et al. Astrocytic Orosomucoid-2 Modulates Microglial Activation and Neuroinflammation. J. Neurosci. 37, 2878–2894 (2017).
pubmed: 28193696
pmcid: 6596722
doi: 10.1523/JNEUROSCI.2534-16.2017
Luo, Z. et al. Orosomucoid, an acute response protein with multiple modulating activities. J. Physiol. Biochem 71, 329–340 (2015).
pubmed: 25711902
doi: 10.1007/s13105-015-0389-9
Biswas, S. K. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxid. Med Cell Longev. 2016, 5698931 (2016).
pubmed: 26881031
pmcid: 4736408
doi: 10.1155/2016/5698931
Leung, L. L. K., J. Morser, J. Carboxypeptidase B2 and carboxypeptidase N in the crosstalk between coagulation, thrombosis, inflammation, and innate immunity. J. Thromb. Haemost., 16, 1474–1486 (2018).
Zhou, Q. et al. Both plasma basic carboxypeptidases, carboxypeptidase B2 and carboxypeptidase N, regulate vascular leakage activity in mice. J. Thromb. Haemost. 20, 238–244 (2022).
pubmed: 34626062
doi: 10.1111/jth.15551
Liu, Y. et al. Overexpression of zinc-α2-glycoprotein suppressed seizures and seizure-related neuroflammation in pentylenetetrazol-kindled rats. J. Neuroinflammation 15, 92 (2018).
pubmed: 29566716
pmcid: 5863804
doi: 10.1186/s12974-018-1132-6
Stipanuk, M. H. et al. Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J. Nutr. 136, 1652s–1659s (2006).
pubmed: 16702335
doi: 10.1093/jn/136.6.1652S
Kimani, S. et al. Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity. Springerplus 2, 647 (2013).
pubmed: 24349951
pmcid: 3862856
doi: 10.1186/2193-1801-2-647
Tor-Agbidye, J. et al. Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa. Brain Res. 820, 12–19 (1999).
pubmed: 10023026
doi: 10.1016/S0006-8993(98)01343-2
Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75, 663–670 (2003).
pubmed: 12585499
doi: 10.1021/ac026117i
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
pubmed: 19029910
doi: 10.1038/nbt.1511
Rohart, F. et al. mixOmics: An R package for ‘omics feature selection and multiple data integration. PLoS Comput Biol. 13, e1005752 (2017).
pubmed: 29099853
pmcid: 5687754
doi: 10.1371/journal.pcbi.1005752
Pino, L. K. et al. The Skyline ecosystem: Informatics for quantitative mass spectrometry proteomics. Mass Spectrom. Rev. 39, 229–244 (2020).