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Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

ABSTRACT: Small admixtures in water, e.g. of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppress cell growth and induce oxidative stress in mitochondria. We thus hypothesize that deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. Because growth acceleration is reduced approximately by half by addition to water a minute amount (0.15%) of 18O isotope, at least part of the deuterium effect on cell growth can be explained by the isotopic resonance phenomenon. A slight (?2-fold) enrichment of deuterium in water accelerates human cell growth. Quantitative MS based proteomics determined changes in protein abundances and redox states and found that deuterium-enriched water acts mainly through decreasing ROS production in mitochondria. This action is opposite to that of deuterium depletion that suppresses cell growth by inducing oxidative stress. Thus deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. The role of isotopic resonance in this effect was validated by further experiments on bacteria.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7664117 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

Zhang Xuepei X Wang Jin J Zubarev Roman A RA

Molecular & cellular proteomics : MCP 20200807 11

Small admixtures in water, <i>e.g.</i> of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppre ...[more]

PMID: 32769093

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Project description:Leaf growth is a complex developmental process that is continuously fine-tuned by the environment. Various abiotic stresses, including mild drought stress, have been shown to inhibit leaf growth in Arabidopsis thaliana (Arabidopsis), but the underlying mechanisms remain largely unknown. Here we identify the redundant Arabidopsis transcription factors ETHYLENE RESPONSE FACTOR 5 (ERF5) and ERF6 as master regulators which adapt leaf growth to environmental changes. ERF5 and ERF6 gene expression is induced very rapidly and specifically in actively growing leaves after sudden exposure to osmotic stress that mimics mild drought. Subsequently, enhanced ERF6 expression inhibits cell proliferation and leaf growth by a process involving GA and DELLA signaling. Using an ERF6 inducible overexpression line, we demonstrate that the GA-degrading enzyme GA2-OX6 is transcriptionally induced by ERF6 and that consequently DELLA proteins are stabilized. As a result, ERF6 gain-of-function lines are dwarfed and hypersensitive to osmotic stress, while growth of erf5erf6 loss-of-function mutants is less affected by stress. Next to its role in plant growth under stress, ERF6 also activates the expression of a plethora of osmotic stress-responsive genes, including the well-known stress tolerance genes STZ, MYB51 and WRKY33. Interestingly, the activation of the stress tolerance genes by ERF6 occurs independently from the ERF6-mediated growth inhibition. Together, these data fit into a leaf growth regulatory model in which ERF5 and ERF6 form a missing link between the previously observed stress-induced 1-aminocyclopropane-1-carboxylic acid (ACC) accumulation and DELLA-mediated cell cycle exit and execute a dual role by regulating both stress tolerance and growth-inhibition. Samples were obtained from three independent experiments and from multiple plates within the experiment. Whole seedlings were harvested rapidly in an excess of RNAlaterÂ® solution (Ambion), and after overnight storage at 4Â°C, dissected under a binocular microscope on a cooling plate with precision microscissors. Dissected leaves were transferred to a new tube, frozen in liquid nitrogen, and ground with a Retsch machine and 3-mm metal balls. RNA was extracted with TriZol (Invitrogen) and further purified with the RNeasy Mini Kit (Qiagen). DNA digestion was done on columns with RNase-free DNase I (Roche). For the identification of genome-wide expression changes, samples of the strong ERF6-overexpressing line (ERF6IOE-S) and the control line (GFP:IOE) were harvested 4Â h after transfer to DEX. Two Âµg of pure RNA samples were hybridized to AGRONOMICS1 Arabidopsis Tiling Arrays (Rehrauer et al., 2010) at the VIB Microarray Facility (Leuven, Belgium).

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Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

Publications

Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

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