[49] Deuteration as a tool in investigating the role of water in the structure and function of excitable membranes

Vasilescu, V.; Katona, Eva

doi:10.1016/0076-6879(86)27052-4

Cited by 15 publications

(7 citation statements)

References 18 publications

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“…However, the effects of D 2 O on microfilament systems, which may be responsible for changes in shape of human neutrophil granulocytes (Zimmermann et al 1988), might also be involved in the effects on platelets. Vasilescu and Katona (1986) found that D 2 O inhibited bioelectrogenesis and contractility in nerve and muscle preparations and uncoupled electrical and mechanical functions in the isolated frog heart. It lowered the ATP/ADP ratio in all these tissues and also played an antagonistic role to anesthetics in sciatic nerve trunks.…”

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

confidence: 96%

“…Among other mechanisms considered (differences in hydration of macromolecules and stabilization of large biopolymers) Vasilescu and Katona (1986) made the interesting suggestion that D functioned less well than H in energy production. This would mean that a deuteron motive force would be less effective than a proton motive force, a possibility that has not, to our knowledge, been tested directly.…”

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

confidence: 99%

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Pharmacological uses and perspectives of heavy water and deuterated compounds

Kushner¹,

Baker²,

Dunstall³

1999

Can. J. Physiol. Pharmacol.

259

177

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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.

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

confidence: 96%

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.

259

177

View full text Add to dashboard Cite

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“…does not inhibit overall cell metabolism, that the inhibition of growth is not due to a reduction of energy supply, and therefore that deuteration of biomolecules should be low and 2H20 should be present in the plant cells mainly as a free exchangeable fraction (13,29).…”

Section: Discussionmentioning

confidence: 99%

“…Incubation in 2H20 of animal and plant tissues and organs has been used extensively for proton density-labeling experiments to study synthesis, degradation, and turnover of proteins (8), to investigate the role of water in the structure and function of biosystems (29), and to suppress solvent signal from the water in proton NMR (11). However, a toxic effect of 2H20 has been observed on growth of Escherichia coli (4), growth and development of plants (2,6,28), and seed germination (12).…”

Section: Plant Materialsmentioning

confidence: 99%

Effects of Deuterium Oxide on Growth, Proton Extrusion, Potassium Influx, and in Vitro Plasma Membrane Activities in Maize Root Segments

Sacchi

Cocucci²

1992

Plant Physiol.

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Elongation of subapical segments of maize (Zea mays) roots was greatly inhibited by 2H20 in the incubation medium. Short-term exposure (30 min) to 2H20 slightly reduced 02 uptake and significantly increased ATP levels. 2H20 inhibited H' extrusion in the presence of both low (0.05 mM) and high (5 mM) external concentrations of K' (about 30 and 53%, respectively at 50% [v/v] 2H20).Experiments on plasma membrane vesicles showed that H+-pumping and ATPase activities were greatly inhibited by 2H20 (about 35% at 50% [v/v] 2H20); NADH-ferricyanide reductase and 1,3-B-glucan synthase activities were inhibited to a lesser extent (less than 15%). ATPase activities present in both the tonoplast-enriched and submitochondrial particle preparations were not affected by 2H20. Therefore, the effect of short incubation time and low concentration of 2H20 is not due to a general action on overall cell metabolism but involves a specific inhibition of the plasma membrane H -ATPase. K+ uptake was inhibited by 2H20 only when K+ was present at a low (0.05 mM) external concentration where absorption is against its electrochemical potential. The transmembrane electric potential difference (Em) was slightly hyperpolarized by 2H20 at low K+, but was not affected at the higher K+ concentrations. These results suggest a relationship between H+ extrusion and K' uptake at low K+ external concentration.plast, probably through a direct or chaotropic effect of 2H20 (7). The effect of 2H20 on membrane functions has not yet been specifically investigated in plant materials. An effect of 2H20 on plant membrane functions might be hypothesized on the basis of the consideration that H+ translocating activities, which play a central role in the function of plant membranes (27), could also utilize 2H' even if to a lesser extent.The experiments described in this paper were aimed at studying the effects of 2H20 on H+ extrusion and related transport activities in subapical maize (Zea mays) root segments. Plasma membrane vesicles of high purity from maize roots were used to compare the in vivo effect of 2H20 on H+ transport with the in vitro effect of 2H20 on H+ pumping and ATPase activities and to clarify whether 2H20 inhibits specifically the H+-translocating activities or membrane activities as a whole. Finally, the possibility of using 2H20 as a tool to investigate the involvement of H+ in membrane transport has been analyzed. MATERIALS AND METHODS Plant MaterialIncubation in 2H20 of animal and plant tissues and organs has been used extensively for proton density-labeling experiments to study synthesis, degradation, and turnover of proteins (8), to investigate the role of water in the structure and function of biosystems (29), and to suppress solvent signal from the water in proton NMR (11). However, a toxic effect of 2H20 has been observed on growth of Escherichia coli (4), growth and development of plants (2,6,28), and seed germination (12). It has been suggested that these effects, obtained at high 2H20 concentrations and after long exposur...

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“…8) An inhibitory effect of D 2 O seems to be due to inhibition of tubulin polymerization and effects on microtubule-organizing centers and other structures governing the formation of the mitotic spindle. [9][10][11] Other effects of D 2 O on energy production, such as lowered ATP/ADP ratios, 12) and on membrane receptors, such as impaired Ca 2ϩ channels and Na ϩ -K ϩ ATPase, have also been reported. [13][14][15] D 2 O also affects heatsensitivity [16][17][18] and the longevity of singlet oxygen.…”

mentioning

confidence: 97%

Increased Expression of Hsp70 for Resistance to Deuterium Oxide in a Yeast Mutant Cell Line

Unno

Kishido

Morioka

et al. 2003

Biological & Pharmaceutical Bulletin

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Labeling with stable isotopes, typically deuterium (D), is powerful tool for studying the functional structure of biomolecules by NMR. Biosynthesis of certain deuterated proteins in microorganisms cultured in deuterium oxide (D(2)O) is an attractive strategy. However, the growth of almost all microorganisms is inhibited at high concentrations of D(2)O. We isolated a mutant of yeast that grows well in D(2)O. The expression of Hsp70 was enhanced in the mutant. The increased expression also endowed the yeast with cold-resistance. The mutant might be useful for biosynthesis of D-labeled biomolecules.

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[49] Deuteration as a tool in investigating the role of water in the structure and function of excitable membranes

Cited by 15 publications

References 18 publications

Pharmacological uses and perspectives of heavy water and deuterated compounds

Pharmacological uses and perspectives of heavy water and deuterated compounds

Effects of Deuterium Oxide on Growth, Proton Extrusion, Potassium Influx, and in Vitro Plasma Membrane Activities in Maize Root Segments

Increased Expression of Hsp70 for Resistance to Deuterium Oxide in a Yeast Mutant Cell Line

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