What is it about?
The presence of bicarbonate in cells acts not only as a pH buffer, but also as a redox buffer by changing the reactivity of Fe(II). In this study, we looked at how DNA and RNA oxidative damage changed as a function of added bicarbonate. We found that with no added bicarbonate, oxidation was extensive and indiscriminate in creating strand breaks and base lesions, likely due to hydroxyl radical. With physiological bicarbonate present, strand breaks were near zero, and base oxidation occurred only on guanine (G), for which a robust system of DNA repair exists. We ascribe the latter to formation of carbonate radical anion, a less reactive radical oxidant.
Featured Image
Photo by digitale.de on Unsplash
Why is it important?
Oxidative stress underlies many cellular processes, and when far out of equilibrium, leads to multiple disorders--cancer, neurological disorders, atherosclerosis, and metabolic diseases--thus, understanding the cellular chemistry that creates oxidative stress is important. Here we show that hydroxyl radical is unlikely to be involved in cellular oxidative stress, contrary to hundreds of published claims in mainstream literature. Instead, a radical derived from carbonate focuses oxidative damage on a single base in DNA (or RNA), namely guanine, and especially on sites of poly-G sequences found in gene regulatory regions. This supports a mechanism in which oxidative modification of specific sites in the genome helps regulate gene expression. In other words, oxidative stress has a convenient feedback mechanism involving DNA damage signaling for a response by the genome.
Perspectives
Bicarbonate is an important component of the growth medium for cells. Researchers studying oxidative stress typically grow cells under a blanket of 5% CO2 which provides a functional level of HCO3- (bicarbonate) to media. However, they often rinse away the media (vitamins, glucose, nutrients) before adding oxidative stress in the form of hydrogen peroxide. These studies fail to give an accurate result because the CO2/HCO3- has bubbled away, and the cellular Fenton reaction then makes the more powerful radical, hydroxyl radical. For years, radiation biologists and nucleic acid chemists have conflated radiation damage to DNA and endogenous oxidative damage to DNA (the latter from Fe(II) + H2O2, the Fenton reaction), but this is incorrect. Ionizing radiation probably does generate hydroxyl radical, but the Fenton reaction in cells does not, at least it does not when physiological bicarbonate is present to redirect the Fenton reaction to formation of a weaker radical.
Cynthia Burrows
University of Utah
Read the Original
This page is a summary of: CO
2
protects cells from iron-Fenton oxidative DNA damage in
Escherichia coli
and humans, Proceedings of the National Academy of Sciences, November 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2419175121.
You can read the full text:
Contributors
The following have contributed to this page
