The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Leon Goldstein - One of the best experts on this subject based on the ideXlab platform.

  • osmotic stress stimulates the organic osmolyte channel in xenopus laevis oocytes expressing skate raja erinacea ae1
    Journal of Experimental Zoology Part A: Comparative Experimental Biology, 2005
    Co-Authors: Danalynn T Koomoa, Mark W Musch, Leon Goldstein
    Abstract:

    The aim of this study was to determine whether hypo-osmolarity, which activates taurine transport through the volume-sensitive organic osmolyte channel in skate (Raja erinacea) erythrocytes, also activates the organic osmolyte channel activity of skate AE1 (skAE1) expressed in oocytes. When Xenopus laevis oocytes expressing skAE1 were incubated in hypo-osmotic ND 96 (210 mOsm) media, taurine was transported at a significantly higher rate than when incubated in ND 96 (235 mOsm), which is iso-osmotic to Xenopus plasma. Therefore, hypo-osmotic stress is part of the activation mechanism of the organic osmolyte channel in skAE1 expressing oocytes. J. Exp. Zool. 303A:319–322, 2005. © 2005 Wiley-Liss, Inc.

  • expression of the skate raja erinacea ae1 osmolyte channel in xenopus laevis oocytes monovalent cation permeability
    The Journal of Membrane Biology, 2004
    Co-Authors: Danalynn T Koomoa, Mark W Musch, D E Myers, Leon Goldstein
    Abstract:

    The aim of this study was to express the cloned skate anion exchanger 1 (skAE1) in Xenopus oocytes and determine whether the differences in monovalent cation permeabilities in hypotonically stimulated skate and trout erythrocytes could be due to differences in the presence or absence of intracellular channel regulators between the two species or in the intrinsic permeability properties of the channels themselves. The expressed protein (skAE1) was inserted into the oocyte cell membrane and facilitated both Cl− exchange and taurine transport. Expression of skAE1 in oocytes showed similar monovalent cation permeabilities as previously reported for skate erythrocytes and different from both trout erythrocytes and trAE1 expressed in Xenopus oocytes. These results show that the skAE1 expressed in oocytes functions in a manner similar to that of the osmolyte channel in hypotonically activated skate erythrocytes and supports the hypothesis that differences in the monovalent cation permeabilities of the osmolyte channels in skate and trout RBCs resides in the differences in permeability properties of the channels between the two species.

Douglas A. Greene - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Glucose on Sorbitol Pathway Activation, Cellular Redox, and Metabolism of myo-lnositol, Phosphoinositide, and Diacylglycerol in Cultured Human Retinal Pigment
    2016
    Co-Authors: Epithelial Cells, Thommey P Thomas, Francesca Porcellati, Koichi Kato, Martin J Stevens, William R Sherman, Douglas A. Greene
    Abstract:

    Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: recipro-cal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD '. The "osmolyte " and "redox " hypotheses pre-dict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis, but through dif-ferent mechanisms: the "osmolyte " hypothesis via depletion of intracellular myo-inositol (the cosubstrate for phosphatidylino-sitolsynthase) and the "redox " hypothesis through enhanced de novo synthesis from triose phosphates. The osmolyte hy-pothesis predicts diminished phosphoinositide-derived arachi-donyldiacylglycerol, while the redox hypothesis predicts in-creased total diacylglycerol and phosphatidic acid. In high al-dose reductase expressing retinal pigment epithelial cells, glucose-induced, aldose reductase inhibitor-sensitive CDP-di-glyceride accumulation and inhibition of 32P-incorporation into phosphatidylinositol paralleled myo-inositol depletion (but not cytoplasmic redox, that was unaffected by glucose) and deple-tion of arachidonyl-diacylglycerol. 3mM pyruvate added to the culture medium left cellular redox unaltered, but stimulated Na+-dependent myo-inositol uptake, accumulation, and incor-poration into phosphatidylinositol. These results favor myo-in-ositol depletion rather than altered redox as the primary cause ofglucose-induced aldose reductase-related defects in phospho-lipid metabolism in cultured retinal pigment epithelial cells. (J

  • effects of glucose on sorbitol pathway activation cellular redox and metabolism of myo inositol phosphoinositide and diacylglycerol in cultured human retinal pigment epithelial cells
    Journal of Clinical Investigation, 1994
    Co-Authors: Thommey P Thomas, Francesca Porcellati, Koichi Kato, Martin J Stevens, William R Sherman, Douglas A. Greene
    Abstract:

    Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: reciprocal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD+. The "osmolyte" and "redox" hypotheses predict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis, but through different mechanisms: the "osmolyte" hypothesis via depletion of intracellular myo-inositol (the cosubstrate for phosphatidylinositol-synthase) and the "redox" hypothesis through enhanced de novo synthesis from triose phosphates. The osmolyte hypothesis predicts diminished phosphoinositide-derived arachidonyl-diacylglycerol, while the redox hypothesis predicts increased total diacylglycerol and phosphatidic acid. In high aldose reductase expressing retinal pigment epithelial cells, glucose-induced, aldose reductase inhibitor-sensitive CDP-diglyceride accumulation and inhibition of 32P-incorporation into phosphatidylinositol paralleled myo-inositol depletion (but not cytoplasmic redox, that was unaffected by glucose) and depletion of arachidonyl-diacylglycerol. 3 mM pyruvate added to the culture medium left cellular redox unaltered, but stimulated Na(+)-dependent myo-inositol uptake, accumulation, and incorporation into phosphatidylinositol. These results favor myo-inositol depletion rather than altered redox as the primary cause of glucose-induced aldose reductase-related defects in phospholipid metabolism in cultured retinal pigment epithelial cells.

  • osmotically induced nerve taurine depletion and the compatible osmolyte hypothesis in experimental diabetic neuropathy in the rat
    Diabetologia, 1993
    Co-Authors: M J Stevens, Carol Van Huysen, Mikiko Kamijo, Anders A F Sima, Sarah A Lattimer, Douglas A. Greene
    Abstract:

    Diabetic neuropathy results from progressive nerve fibre damage with blunted nerve regeneration and repair and may be complicated by nerve hyperexcitability resulting in pain. The naturally occurring amino acid taurine functions as an osmolyte, inhibitory neurotransmitter, and modulator of pain perception. It is also known to have neurotrophic actions. The compatible osmolyte hypothesis proposes that levels of intracellular organic osmolytes including taurine and myo-inositol, respond co-ordinately in response to changes in intracellular sorbitol or external osmolality to maintain the intracellular milieu. We hypothesize that glucose-induced sorbitol accumulation in diabetes mellitus will result in taurine depletion in peripheral nerve which may potentially impair nerve regeneration and precipitate neuronal hyperexcitability and pain. This study explored the relationships of taurine, myo-inositol and sorbitol in the rat nerve and their effects on nerve conduction velocity. Osmolyte levels and nerve conduction velocity were determined in sciatic nerve from non-diabetic and streptozotocin-induced diabetic rats, with or without dietary taurine or myo-inositol supplementation. Taurine levels decreased by 31% (p< 0.01) and myo-inositol decreased by 37% (p<0.05) in diabetic nerve as sorbitol accumulated. Taurine supplementation of diabetic animals did not affect nerve conduction velocity but further reduced nerve myo-inositol levels. Prevention of sorbitol accumulation with the aldose reductase inhibitor sorbinil increased nerve taurine levels by 22% (p<0.05) when compared with untreated diabetic animals. Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one osmolyte results in reciprocal depletion of others. Diabetic neuropathy may be an example of maladaptive osmoregulation, nerve damage and instability being aggravated by taurine depletion.

Joanemma Shea - One of the best experts on this subject based on the ideXlab platform.

  • trimethylamine n oxide counteracts urea denaturation by inhibiting protein urea preferential interaction
    Journal of the American Chemical Society, 2018
    Co-Authors: Pritam Ganguly, Pablo Oserma, Nico F A Van Der Veg, Joanemma Shea
    Abstract:

    Osmolytes are small organic molecules that can modulate the stability and function of cellular proteins by altering the chemical environment of the cell. Some of these osmolytes work in conjunction, via mechanisms that are poorly understood. An example is the naturally occurring protein-protective osmolyte trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine organisms against the detrimental denaturing effects of another naturally occurring osmolyte, urea. From a computational standpoint, our understanding of this counteraction mechanism is hampered by the fact that existing force fields fail to capture the correct balance of TMAO and urea interactions in ternary solutions. Using molecular dynamics simulations and Kirkwood–Buff theory of solutions, we have developed an optimized force field that reproduces experimental Kirkwood–Buff integrals. We show through the study of two model systems, a 15-residue polyalanine chain and the R2-fragment (273GKVQIINKKLDL284) of the Tau protein, tha...

  • trimethylamine n oxide counteracts urea denaturation by inhibiting protein urea preferential interaction
    Journal of the American Chemical Society, 2018
    Co-Authors: Pritam Ganguly, Pablo Boserman, Nico F A Van Der Vegt, Joanemma Shea
    Abstract:

    Osmolytes are small organic molecules that can modulate the stability and function of cellular proteins by altering the chemical environment of the cell. Some of these osmolytes work in conjunction, via mechanisms that are poorly understood. An example is the naturally occurring protein-protective osmolyte trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine organisms against the detrimental denaturing effects of another naturally occurring osmolyte, urea. From a computational standpoint, our understanding of this counteraction mechanism is hampered by the fact that existing force fields fail to capture the correct balance of TMAO and urea interactions in ternary solutions. Using molecular dynamics simulations and Kirkwood-Buff theory of solutions, we have developed an optimized force field that reproduces experimental Kirkwood-Buff integrals. We show through the study of two model systems, a 15-residue polyalanine chain and the R2-fragment (273GKVQIINKKLDL284) of the Tau protein, that TMAO can counteract the denaturing effects of urea by inhibiting protein-urea preferential interaction. The extent to which counteraction can occur is seen to depend heavily on the amino acid composition of the peptide.

  • mutual exclusion of urea and trimethylamine n oxide from amino acids in mixed solvent environment
    Journal of Physical Chemistry Letters, 2015
    Co-Authors: Pritam Ganguly, Joanemma Shea, Timir Hajari, Nico F. A. Van Der Vegt
    Abstract:

    We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood–Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte–osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO–water interactions, as observed with different TMAO force fields.

  • Mutual Exclusion of Urea and Trimethylamine N‑Oxide from Amino Acids in Mixed Solvent Environment
    2015
    Co-Authors: Pritam Ganguly, Joanemma Shea, Timir Hajari, Nico F. A. Van Der Vegt
    Abstract:

    We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood–Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte–osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO–water interactions, as observed with different TMAO force fields

Danalynn T Koomoa - One of the best experts on this subject based on the ideXlab platform.

  • osmotic stress stimulates the organic osmolyte channel in xenopus laevis oocytes expressing skate raja erinacea ae1
    Journal of Experimental Zoology Part A: Comparative Experimental Biology, 2005
    Co-Authors: Danalynn T Koomoa, Mark W Musch, Leon Goldstein
    Abstract:

    The aim of this study was to determine whether hypo-osmolarity, which activates taurine transport through the volume-sensitive organic osmolyte channel in skate (Raja erinacea) erythrocytes, also activates the organic osmolyte channel activity of skate AE1 (skAE1) expressed in oocytes. When Xenopus laevis oocytes expressing skAE1 were incubated in hypo-osmotic ND 96 (210 mOsm) media, taurine was transported at a significantly higher rate than when incubated in ND 96 (235 mOsm), which is iso-osmotic to Xenopus plasma. Therefore, hypo-osmotic stress is part of the activation mechanism of the organic osmolyte channel in skAE1 expressing oocytes. J. Exp. Zool. 303A:319–322, 2005. © 2005 Wiley-Liss, Inc.

  • expression of the skate raja erinacea ae1 osmolyte channel in xenopus laevis oocytes monovalent cation permeability
    The Journal of Membrane Biology, 2004
    Co-Authors: Danalynn T Koomoa, Mark W Musch, D E Myers, Leon Goldstein
    Abstract:

    The aim of this study was to express the cloned skate anion exchanger 1 (skAE1) in Xenopus oocytes and determine whether the differences in monovalent cation permeabilities in hypotonically stimulated skate and trout erythrocytes could be due to differences in the presence or absence of intracellular channel regulators between the two species or in the intrinsic permeability properties of the channels themselves. The expressed protein (skAE1) was inserted into the oocyte cell membrane and facilitated both Cl− exchange and taurine transport. Expression of skAE1 in oocytes showed similar monovalent cation permeabilities as previously reported for skate erythrocytes and different from both trout erythrocytes and trAE1 expressed in Xenopus oocytes. These results show that the skAE1 expressed in oocytes functions in a manner similar to that of the osmolyte channel in hypotonically activated skate erythrocytes and supports the hypothesis that differences in the monovalent cation permeabilities of the osmolyte channels in skate and trout RBCs resides in the differences in permeability properties of the channels between the two species.

Pritam Ganguly - One of the best experts on this subject based on the ideXlab platform.

  • trimethylamine n oxide counteracts urea denaturation by inhibiting protein urea preferential interaction
    Journal of the American Chemical Society, 2018
    Co-Authors: Pritam Ganguly, Pablo Oserma, Nico F A Van Der Veg, Joanemma Shea
    Abstract:

    Osmolytes are small organic molecules that can modulate the stability and function of cellular proteins by altering the chemical environment of the cell. Some of these osmolytes work in conjunction, via mechanisms that are poorly understood. An example is the naturally occurring protein-protective osmolyte trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine organisms against the detrimental denaturing effects of another naturally occurring osmolyte, urea. From a computational standpoint, our understanding of this counteraction mechanism is hampered by the fact that existing force fields fail to capture the correct balance of TMAO and urea interactions in ternary solutions. Using molecular dynamics simulations and Kirkwood–Buff theory of solutions, we have developed an optimized force field that reproduces experimental Kirkwood–Buff integrals. We show through the study of two model systems, a 15-residue polyalanine chain and the R2-fragment (273GKVQIINKKLDL284) of the Tau protein, tha...

  • trimethylamine n oxide counteracts urea denaturation by inhibiting protein urea preferential interaction
    Journal of the American Chemical Society, 2018
    Co-Authors: Pritam Ganguly, Pablo Boserman, Nico F A Van Der Vegt, Joanemma Shea
    Abstract:

    Osmolytes are small organic molecules that can modulate the stability and function of cellular proteins by altering the chemical environment of the cell. Some of these osmolytes work in conjunction, via mechanisms that are poorly understood. An example is the naturally occurring protein-protective osmolyte trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine organisms against the detrimental denaturing effects of another naturally occurring osmolyte, urea. From a computational standpoint, our understanding of this counteraction mechanism is hampered by the fact that existing force fields fail to capture the correct balance of TMAO and urea interactions in ternary solutions. Using molecular dynamics simulations and Kirkwood-Buff theory of solutions, we have developed an optimized force field that reproduces experimental Kirkwood-Buff integrals. We show through the study of two model systems, a 15-residue polyalanine chain and the R2-fragment (273GKVQIINKKLDL284) of the Tau protein, that TMAO can counteract the denaturing effects of urea by inhibiting protein-urea preferential interaction. The extent to which counteraction can occur is seen to depend heavily on the amino acid composition of the peptide.

  • mutual exclusion of urea and trimethylamine n oxide from amino acids in mixed solvent environment
    Journal of Physical Chemistry Letters, 2015
    Co-Authors: Pritam Ganguly, Joanemma Shea, Timir Hajari, Nico F. A. Van Der Vegt
    Abstract:

    We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood–Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte–osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO–water interactions, as observed with different TMAO force fields.

  • Mutual Exclusion of Urea and Trimethylamine N‑Oxide from Amino Acids in Mixed Solvent Environment
    2015
    Co-Authors: Pritam Ganguly, Joanemma Shea, Timir Hajari, Nico F. A. Van Der Vegt
    Abstract:

    We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood–Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte–osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO–water interactions, as observed with different TMAO force fields