The Role of Redox Cycling Versus Arylation in Quinone-Induced Mitochondrial Dysfunction: A Mechanistic Approach in Classifying Reactive Toxicants

T. R. Henry, Kendall B Wallace

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In an attempt to distinguish between the mechanisms by which electrophilic and redox cycling quinones induce the cyclosporine A (CyA)-sensitive mitochondrial membrane permeability transition, the ability of a series of quinones that span a broad range of electrophilic and redox cycling reactivities has been examined. The order of potency of quinone-induced Ca2+ release was 1,4-naphthoquinone (NQ) > 1,4-benzoquinone (BQ) > 2-methyl-1,4-naphthoquinone (MQ) > 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ) > 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ), Quinones with predominantly redox cycling reactivity, NQ (< 4pM), MQ, DiOMeNQ and DiMeNQ, induced the CyA-sensitive membrane permeability transition. In contrast, NQ (>4pM) and BQ, induced rapid and complete Ca2+ release and membrane depolarization, but not swelling. Furthermore, BQ and NQ (> 4 pM)-induced effects were not prevented by CyA. Therefore, we maintain that, unlike MQ, DiOMeNQ, DiMeNQ and NQ (<4pM), effects of BQ and NQ(>4pM) on calcium flux and membrane potential are manifest via a mechanism independent of altering the regulation of the cyclosporine A-sensitive PTP. These findings suggest that stereoelectronic descriptors for soft electrophilicity and one electron reduction potential may be useful in differentiating and predicting mechanisms of quinone toxicity.

Original languageEnglish (US)
Pages (from-to)97-108
Number of pages12
JournalSAR and QSAR in environmental research
Volume4
Issue number2-3
DOIs
StatePublished - Dec 1 1995

Keywords

  • Quinone toxicity
  • arylation
  • mechanisms of toxic action
  • mitochondria
  • permeability transition
  • redox cycling

Fingerprint Dive into the research topics of 'The Role of Redox Cycling Versus Arylation in Quinone-Induced Mitochondrial Dysfunction: A Mechanistic Approach in Classifying Reactive Toxicants'. Together they form a unique fingerprint.

Cite this