Abstract Title:

Mitochondrial ascorbic acid is responsible for enhanced susceptibility of U937 cells to the toxic effects of peroxynitrite.

Abstract Source:

Biofactors. 2014 Mar-Apr;40(2):236-46. Epub 2013 Sep 16. PMID: 24105898

Abstract Author(s):

Andrea Guidarelli, Liana Cerioni, Mara Fiorani, Catia Azzolini, Orazio Cantoni

Article Affiliation:

Andrea Guidarelli


Otherwise nontoxic levels of peroxynitrite promote toxicity in U937 cells pre-exposed to low micromolar concentrations of l-ascorbic acid (AA). This event was associated with the mitochondrial accumulation of the vitamin and with the early formation of secondary reactive oxygen species and DNA single-strand breaks. The same concentrations of peroxynitrite, however, failed to elicit detectable effects in cells pre-exposed to dehydroascorbic acid (DHA), in which mitochondrial accumulation of vitamin C did not occur despite the identical cytosolic levels. Coherently, oxidation of extracellular AA failed to affect the intracellular concentration of the vitamin, but nevertheless prevented its mitochondrial localization as well as the enhanced response to peroxynitrite. Furthermore, in cells postincubated in vitamin C-free medium, time-dependent loss of mitochondrial AA was paralleled by a progressive decline of susceptibility to peroxynitrite, under the same conditions in which cells retained about half of the initial AA. Using different experimental approaches, we finally showed that the enhancing effects of AA are mediated by events associated with peroxynitrite-dependent superoxide/H2 O2 formation in the mitochondrial respiratory chain. Collectively, these results indicate that mitochondria actively take up vitamin C as AA and respond to otherwise inactive concentrations of peroxynitrite with the mitochondrial formation of secondary species responsible for DNA damage and toxicity. DHA preloading, while leading to the accumulation of identical levels of vitamin C, fails to produce these effects because of the poor mitochondrial accumulation of the vitamin.

Study Type : In Vitro Study

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.