Inactivation of Glyceraldehyde-3-phosphate Dehydrogenase by the Dopamine Metabolite, 3,4-dihydroxyphenylacetaldehyde

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2017 Aug 24

PMID 28830811

Citations 17

Authors

Brigitte C Vanle

Virginia R Florang

Daryl J Murry

Arturo L Aguirre

Jonathan A Doorn

Affiliations

Soon will be listed here.

Abstract

Background: The aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL) is an endogenous neurotoxin implicated in Parkinson's Disease. Elucidating protein targets of DOPAL is essential in understanding it's pathology. The enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a target of DOPAL.

Methods: GAPDH activity was measured via reduction of NAD cofactor (340 nm). Protein aggregation was assessed with SDS-PAGE methods and specific modification via chemical probes.

Results: Low micromolar levels of DOPAL caused extensive GAPDH aggregation and irreversibly inhibited enzyme activity. The inactivation of GAPDH was dependent on both the catechol and aldehyde moieties of DOPAL. It is suggested that Cys are modified and oxidized by DOPAL.

Conclusions: The mechanism by which DOPAL modifies GAPDH can serve as a mechanistic explanation to the pathological events in Parkinson's Disease.

Citing Articles

Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.

Currim F, Tanwar R, Brown-Leung J, Paranjape N, Liu J, Sanders L Neurotoxicology. 2024; 103:266-287.

PMID: 38964509 PMC: 11288778. DOI: 10.1016/j.neuro.2024.06.016.

Sequestosome-1 (SQSTM1/p62) as a target in dopamine catabolite-mediated cellular dyshomeostasis.

Masato A, Andolfo A, Favetta G, Bellini E, Cogo S, Dalla Valle L Cell Death Dis. 2024; 15(6):424.

PMID: 38890356 PMC: 11189528. DOI: 10.1038/s41419-024-06763-x.

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.

Ratan Y, Rajput A, Pareek A, Pareek A, Jain V, Sonia S Biomolecules. 2024; 14(1).

PMID: 38254673 PMC: 10813470. DOI: 10.3390/biom14010073.

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.

Jin X, Si X, Lei X, Liu H, Shao A, Li L Aging Dis. 2023; 15(3):1204-1226.

PMID: 37815908 PMC: 11081171. DOI: 10.14336/AD.2023.0821-2.

Role of dopamine in the pathophysiology of Parkinson's disease.

Zhou Z, Yi L, Wang D, Lim T, Tan E Transl Neurodegener. 2023; 12(1):44.

PMID: 37718439 PMC: 10506345. DOI: 10.1186/s40035-023-00378-6.

References

Follmer C, Coelho-Cerqueira E, Yatabe-Franco D, Araujo G, Pinheiro A, Domont G . Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of α-Synuclein with the Toxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL). J Biol Chem. 2015; 290(46):27660-79. PMC: 4646016. DOI: 10.1074/jbc.M115.686584. View

Rees J, Florang V, Eckert L, Doorn J . Protein reactivity of 3,4-dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol. Chem Res Toxicol. 2009; 22(7):1256-63. PMC: 2717024. DOI: 10.1021/tx9000557. View

Olah J, Tokesi N, Vincze O, Horvath I, Lehotzky A, Erdei A . Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and their co-localization in Lewy bodies. FEBS Lett. 2006; 580(25):5807-14. DOI: 10.1016/j.febslet.2006.09.037. View

Park J, MERIWETHER B, CLODFELDER P, CUNNINGHAM L . The hydrolysis of p-nitrophenyl acetate catalyzed by 3-phosphoglyceraldehyde dehydrogenase. J Biol Chem. 1961; 236:136-41. View

Burke W, Li S, Chung H, Ruggiero D, Kristal B, Johnson E . Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. Neurotoxicology. 2003; 25(1-2):101-15. DOI: 10.1016/S0161-813X(03)00090-1. View

Helander A, Tottmar O . Reactions of biogenic aldehydes with hemoglobin. Alcohol. 1989; 6(1):71-5. DOI: 10.1016/0741-8329(89)90076-1. View

Nakajima H, Amano W, Fukuhara A, Kubo T, Misaki S, Azuma Y . An aggregate-prone mutant of human glyceraldehyde-3-phosphate dehydrogenase augments oxidative stress-induced cell death in SH-SY5Y cells. Biochem Biophys Res Commun. 2009; 390(3):1066-71. DOI: 10.1016/j.bbrc.2009.10.118. View

Uchida K, Stadtman E . Covalent attachment of 4-hydroxynonenal to glyceraldehyde-3-phosphate dehydrogenase. A possible involvement of intra- and intermolecular cross-linking reaction. J Biol Chem. 1993; 268(9):6388-93. View

Burke W, Kumar V, Pandey N, Panneton W, Gan Q, Franko M . Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol. 2007; 115(2):193-203. DOI: 10.1007/s00401-007-0303-9. View

10.

BURKE W, Chung H, Li S . Quantitation of 3,4-dihydroxyphenylacetaldehyde and 3, 4-dihydroxyphenylglycolaldehyde, the monoamine oxidase metabolites of dopamine and noradrenaline, in human tissues by microcolumn high-performance liquid chromatography. Anal Biochem. 1999; 273(1):111-6. DOI: 10.1006/abio.1999.4196. View

11.

Ishii T, Sunami O, Nakajima H, Nishio H, Takeuchi T, Hata F . Critical role of sulfenic acid formation of thiols in the inactivation of glyceraldehyde-3-phosphate dehydrogenase by nitric oxide. Biochem Pharmacol. 1999; 58(1):133-43. DOI: 10.1016/s0006-2952(99)00060-x. View

12.

Nilsson G, Tottmar O . Biogenic aldehydes in brain: on their preparation and reactions with rat brain tissue. J Neurochem. 1987; 48(5):1566-72. DOI: 10.1111/j.1471-4159.1987.tb05702.x. View

13.

Ungar F, Tabakoff B, ALIVISATOS S . Inhibition of binding of aldehydes of biogenic amines in tissues. Biochem Pharmacol. 1973; 22(15):1905-13. DOI: 10.1016/0006-2952(73)90050-6. View

14.

Marsden C . Dopamine: the rewarding years. Br J Pharmacol. 2006; 147 Suppl 1:S136-44. PMC: 1760752. DOI: 10.1038/sj.bjp.0706473. View

15.

Ross C, Poirier M . Protein aggregation and neurodegenerative disease. Nat Med. 2004; 10 Suppl:S10-7. DOI: 10.1038/nm1066. View

16.

Mazzola J, Sirover M . Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders?. Neurotoxicology. 2002; 23(4-5):603-9. DOI: 10.1016/s0161-813x(02)00062-1. View

17.

Anderson D, Mariappan S, Buettner G, Doorn J . Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone. J Biol Chem. 2011; 286(30):26978-86. PMC: 3143656. DOI: 10.1074/jbc.M111.249532. View

18.

Jinsmaa Y, Sullivan P, Gross D, Cooney A, Sharabi Y, Goldstein D . Divalent metal ions enhance DOPAL-induced oligomerization of alpha-synuclein. Neurosci Lett. 2014; 569:27-32. PMC: 4061610. DOI: 10.1016/j.neulet.2014.03.016. View

19.

Martyniuk C, Fang B, Koomen J, Gavin T, Zhang L, Barber D . Molecular mechanism of glyceraldehyde-3-phosphate dehydrogenase inactivation by α,β-unsaturated carbonyl derivatives. Chem Res Toxicol. 2011; 24(12):2302-11. PMC: 3243798. DOI: 10.1021/tx200437y. View

20.

Tatton N . Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp Neurol. 2000; 166(1):29-43. DOI: 10.1006/exnr.2000.7489. View