Thiol-reactivity of the fungicide maneb

• Type of Material: Article
• Authors: James R. Roede, Emory University; Dean P Jones, Emory University
• Language: English
• Date: 2014
• Publisher: Elsevier: Creative Commons
• Publication Version: Final Published Version
• Copyright Statement: © 2014 The Authors
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.journals.elsevier.com/redox-biology
• Title of Journal or Parent Work: Redox Biology
• ISSN: 2213-2317
• Volume: 2
• Issue: 2014
• Start Page: 651
• End Page: 655
• Grant/Funding Information: This work was supported in part, by grants NIH/NIEHSF32 ES019821 (J.R.R.) and R01 ES009047 (D.P.J.).
• Keywords: Pesticide; Dithiocarbamate; Thiol; Toxicity; Parkinson's disease
• Research Categories: Health Sciences, General

Abstract

Maneb (MB) is a manganese-containing ethylene bis-dithiocarbamate fungicide that is implicated as an environmental risk factor for Parkinson's disease, especially in combination with paraquat (PQ). Dithiocarbamates inhibit aldehyde dehydrogenases, but the relationship of this to the combined toxicity of MB + PQ is unclear because PQ is an oxidant and MB activates Nrf2 and increases cellular GSH without apparent oxidative stress. The present research investigated the direct reactivity of MB with protein thiols using recombinant thioredoxin-1 (Trx1) as a model protein. The results show that MB causes stoichiometric loss of protein thiols, reversibly dimerizes the protein and inhibits its enzymatic activity. MB reacted at similar rates with low-molecular weight, thiol-containing chemicals. Together, the data suggest that MB can potentiate neurotoxicity of multiple agents by disrupting protein thiol functions in a manner analogous to that caused by oxidative stress, but without GSH depletion.