D2O-induced ion channel activation in Characeae at low ionic strength

Anđjus, Pavle R.; Kataev, A. A.; Alexandrov, A. A.; Vũcelić, D.; Berestovsky, G. N.

doi:10.1007/bf00233382

Cited by 16 publications

(9 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of the cell integrity pathway is in agreement with its role in mediating an appropriate response to allow survival during sudden changes in water activity [66] and earlier studies suggesting that D2O causes osmotic stress [67,68]. It does, however, pose the question of how the solvent exchange, or what property of D2O, causes activation of the pathway?…”

Section: Discussionsupporting

confidence: 81%

Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

et al. 2020

View full text Add to dashboard Cite

Since life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O), and investigated the biological effects by a wide range of techniques, using the fission yeast Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that D2O causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several D2O sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genes pmk1, mkh1, pek1 and pck2, that control cell wall biogenesis, were more tolerant to D2O. We speculate that D2O affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the D2O-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects..

show abstract

Section: Discussionsupporting

confidence: 81%

Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

et al. 2020

View full text Add to dashboard Cite

show abstract

“…D 2 O has a number of other effects on membrane function, including membrane depolarization and activation of Ca 2+ channels in algae, inhibition of Na + -K + ATPase in animal membranes and interference with Cl --HCO 3 exchange in liver cells (Andjus and Vucelic 1990;Andjus et al 1994;Elsing et al 1995). These effects do not seem to have been studied in depth.…”

Section: Effects Of D 2 O On Proteins Cells and Tissuesmentioning

confidence: 99%

Pharmacological uses and perspectives of heavy water and deuterated compounds

Kushner¹,

Baker²,

Dunstall³

1999

Can. J. Physiol. Pharmacol.

256

177

View full text Add to dashboard Cite

Since the discovery of D20 (heavy water) and its use as a moderator in nuclear reactors, its biological effects have been extensively, although seldom deeply, studied. This article reviews these effects on whole animals, animal cells, and microorganisms. Both "solvent isotope effects," those due to the special properties of D20 as a solvent, and "deuterium isotope effects" (DIE), which result when D replaces H in many biological molecules, are considered. The low toxicity of D20 toward mammals is reflected in its widespread use for measuring water spaces in humans and other animals. Higher concentrations (usually >20% of body weight) can be toxic to animals and animal cells. Effects on the nervous system and the liver and on formation of different blood cells have been noted. At the cellular level, D20 may affect mitosis and membrane function. Protozoa are able to withstand up to 70% D20. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources of a large number of deuterated molecules. D2O increases heat stability of macromolecules but may decrease cellular heat stability, possibly as a result of inhibition of chaperonin formation. High D2O concentrations can reduce salt- and ethanol-induced hypertension in rats and protect mice from gamma irradation. Such concentrations are also used in boron neutron capture therapy to increase neutron penetration to boron compounds bound to malignant cells. D2O is more toxic to malignant than normal animal cells, but at concentrations too high for regular therapeutic use. D2O and deuterated drugs are widely used in studies of metabolism of drugs and toxic substances in humans and other animals. The deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of the anticancer drug tamoxifen and other compounds. Deuteration increases effectiveness of long-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdown by target microorganisms. A few deuterated antibiotics have been prepared, and their antimicrobial activity was found to be little changed. Their action on resistant bacteria has not been studied, but there is no reason to believe that they would be more effective against such bacteria. Insect resistance to insecticides is very often due to insecticide destruction through the cytochrome P450 system. Deuterated insecticides might well be more effective against resistant insects, but this potentially valuable possibility has not yet been studied.

show abstract

“…4,[15][16][17][18][19][20] Better understanding of D 2 O influence on lipid bilayer is provided by experiments using model membranes and theoretical studies. Under physiological conditions, lipid bilayers are immersed in water media and thus fully hydrated.…”

Section: B Effect Of Heavy Water On Phospholipid Bilayers: Longer Lamentioning

confidence: 99%

Does fluoride disrupt hydrogen bond network in cationic lipid bilayer? Time-dependent fluorescence shift of Laurdan and molecular dynamics simulations

Pokorná

Jurkiewicz

Vazdar

et al. 2014

The Journal of Chemical Physics

View full text Add to dashboard Cite

Time-dependent fluorescence shift (TDFS) of Laurdan embedded in phospholipid bilayers reports on hydration and mobility of the phospholipid acylgroups. Exchange of H2O with D2O prolongs the lifetime of lipid-water and lipid-water-lipid interactions, which is reflected in a significantly slower TDFS kinetics. Combining TDFS measurements in H2O and D2O hydrated bilayers with atomistic molecular dynamics (MD) simulations provides a unique tool for characterization of the hydrogen bonding at the acylgroup level of lipid bilayers. In this work, we use this approach to study the influence of fluoride anions on the properties of cationic bilayers composed of trimethylammonium-propane (DOTAP). The results obtained for DOTAP are confronted with those for neutral phosphatidylcholine (DOPC) bilayers. Both in DOTAP and DOPC H2O/D2O exchange prolongs hydrogen-bonding lifetime and does not disturb bilayer structure. These results are confirmed by MD simulations. TDFS experiments show, however, that for DOTAP this effect is cancelled in the presence of fluoride ions. We interpret these results as evidence that strongly hydrated fluoride is able to steal water molecules that bridge lipid carbonyls. Consequently, when attracted to DOTAP bilayer, fluoride disrupts the local hydrogen-bonding network, and the differences in TDFS kinetics between H2O and D2O hydrated bilayers are no longer observed. A distinct behavior of fluoride is also evidenced by MD simulations, which show different lipid-ion binding for Cl(-) and F(-).

show abstract

D2O-induced ion channel activation in Characeae at low ionic strength

Cited by 16 publications

References 25 publications

Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

Pharmacological uses and perspectives of heavy water and deuterated compounds

Does fluoride disrupt hydrogen bond network in cationic lipid bilayer? Time-dependent fluorescence shift of Laurdan and molecular dynamics simulations

Contact Info

Product

Resources

About