Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde

Brigitte C Vanle; Virginia R Florang; Daryl J Murry; Arturo L Aguirre; Jonathan A Doorn

doi:10.1016/j.bbrc.2017.08.067

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Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde

Journal article

Peer reviewed

Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde

Brigitte C Vanle, Virginia R Florang, Daryl J Murry, Arturo L Aguirre and Jonathan A Doorn

Biochemical and biophysical research communications, Vol.492(2), pp.275-281

10/14/2017

DOI: 10.1016/j.bbrc.2017.08.067

PMCID: PMC5746426

PMID: 28830811

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https://www.ncbi.nlm.nih.gov/pmc/articles/5746426View

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Abstract

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

Protein Aggregates

Rabbits

3,4-Dihydroxyphenylacetic Acid - metabolism

Animals

Humans

Enzyme Induction

Rats

3,4-Dihydroxyphenylacetic Acid - analogs & derivatives

Parkinson Disease - metabolism

Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism

Dopamine - metabolism

Glyceraldehyde-3-Phosphate Dehydrogenases - chemistry

Details

Title: Subtitle: Inactivation of glyceraldehyde-3-phosphate dehydrogenase by the dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde
Creators: Brigitte C Vanle - Department of Pharmaceutical Sciences and Experimental Therapeutics, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Ave, Iowa City, IA 52242-1112, United States
Virginia R Florang - Department of Pharmaceutical Sciences and Experimental Therapeutics, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Ave, Iowa City, IA 52242-1112, United States
Daryl J Murry - Department of Pharmaceutical Sciences and Experimental Therapeutics, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Ave, Iowa City, IA 52242-1112, United States
Arturo L Aguirre - Department of Pharmaceutical Sciences and Experimental Therapeutics, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Ave, Iowa City, IA 52242-1112, United States
Jonathan A Doorn - Department of Pharmaceutical Sciences and Experimental Therapeutics, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, 115 South Grand Ave, Iowa City, IA 52242-1112, United States. Electronic address: jonathan-doorn@uiowa.edu
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.492(2), pp.275-281
DOI: 10.1016/j.bbrc.2017.08.067
PMID: 28830811
PMCID: PMC5746426
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: United States
Grant note: T32 GM067795 / NIGMS NIH HHS R25 GM058939 / NIGMS NIH HHS P30 ES005605 / NIEHS NIH HHS R01 ES015507 / NIEHS NIH HHS T32 GM008365 / NIGMS NIH HHS
Language: English
Date published: 10/14/2017
Academic Unit: Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Medicinal and Natural Products Chemistry
Record Identifier: 9984065386602771

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