| 41. |
- Peleli, Maria, et al.
(författare)
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Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis
- 2016
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 310:1, s. F43-F56
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Tidskriftsartikel (refereegranskat)abstract
- Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal excretion pattern, NOX activity and expression, as well as components of RAAS were characterized. On normal salt diet, PUUO rats had elevated blood pressure compared with controls (115±3 vs 87±1 mmHg), and displayed increased urine production and lower urine osmolality. Blood pressure change in response to salt loading (salt-sensitivity) was more pronounced in the PUUO group compared with controls (15±2 vs 5±1mmHg). Renal denervation in PUUO rats attenuated hypertension (97±3mmHg) and salt-sensitivity (5±1mmHg), and normalized renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression, as well as renin and AT1A receptor expression, were increased in renal cortex from PUUO rats, and normalized by denervation. Plasma sodium and potassium levels were elevated in PUUO rats and normalized after renal denervation. Denervation in PUUO rats was also associated with reduced NOX expression, superoxide production and fibrosis in the heart. This study emphasizes a link between renal nerves, NOX function, and development of hypertension.
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| 42. |
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| 43. |
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| 44. |
- Roine, Jesper
(författare)
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Rysslands ekonomiska framtid
- 2022
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Ingår i: Tidskriften Essä. - : Tidskriften Essä. - 2002-9853. - 9789198753530 ; , s. 48-62
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 45. |
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| 46. |
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| 47. |
- Sellin, Siv, 1935-
(författare)
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The use of metal substitution in characterizing the catalytic mechanism of glyoxalase I
- 1983
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glyoxalase I, a zinc enzyme, has been purified from human erythrocytes. The aim of this investigation was to examine the active center of this enzyme and its catalytic mechanism by applying different spectroscopic methods to the study of metal-substituted glyoxalase I. A method has been developed for preparing metal-free and inactive enzyme, which can be reactivated with various divalent metal ions. A metal content of two metal ions per enzyme dimer was determined using atomic absorption spectroscopy. Strong binding of the divalent metal ions to the protein was established by the determination of the dissociation constants.Kinetic parameters for native zinc(II)-glyoxalase I and enzyme reactivated with magnesium(II), cobalt(II) and manganese(ll) were of similar magnitude. It was discovered that the glyoxalase I reaction is reversible and the equilibrium constant was determined.S-substituted derivatives of the cofactor glutathione have been prepared and they are all competitive inhibitors of the enzyme. The fluorescence of tryptophan in the protein was partially quenched by addition of glutathione derivatives, a phenomenon that has been used in binding studies.The metal in glyoxalase I demonstrates hexa-coordination as indicated by the properties of the visible absorption spectrum and electronic paramagnetic spectrum of cobalt(II)- glyoxalase I.The paramagnetic effect of manganese ions bound to the enzyme on the nuclear relaxation rate of water protons has been used to determine the number of rapidly exchanging water molecules bound to the metal in the enzyme. This number turned out to- be equal to two. Binding of glutathione derivatives decreased the relaxation rate of water protons by immobilizing one of the water molecules. This effect is due to the sulfur substituent on glutathione, since no effect could be observed with glutathione itself.The position and the conformation of substrate analogs and certain other S-substituted glutathione derivatives in the active site have been obtained from proton- and carbon-13- nuclear magnetic resonance studies of these compounds interacting with paramagnetic manganese(II)- and cobalt(II)-glyoxalase I. Most glutathione derivatives were found to have an extended shape and to bind to the metal via an invervening water molecule.The essential metal of glyoxalase I has been demonstrated to be situated in the active site, where it probably has both a structural role and a function in catalysis. A mechanism for the glyoxalase I reaction is proposed in which a water ligand of the metal is suggested to polarize the carbonyl group of the substrate and the product by hydrogen bonding. Conformational changes of the enzyme are suggested to accomapny substrate binding and product formation.
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| 48. |
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| 49. |
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