[1] Overview: The Na,K-pump

Skou, J.C.

doi:10.1016/0076-6879(88)56004-4

Cited by 237 publications

(84 citation statements)

References 80 publications

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“…25 This oxidative stress alteration may be responsible for the liver tissue damage caused by cholestasis: an increase in TBARS has been shown to alter membrane functioning, to deregulate glyco- may also be involved in liver damage are alterations in plasma Ca 2/ -ATPase-dependent enzyme, 27 which is needed to mainmembrane fluidity, reduced Na / -K / -ATPase activity, and al-tain membrane permeability and transport functions in terations in cytoskeletal function. 24,27,28 Moreover, all these hepatic cells and probably in other cell types, e.g., erythroalterations are closely related with increased oxidative cytes. 24 The methylation of SAM prevents the inhibition of stress.…”

Section: Discussionmentioning

confidence: 99%

Effects ofS-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats

et al. 1997

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and hepatotoxins. [5][6][7] The drug was also found to decrease We used an animal model of extrahepatic biliary obstrucfibrogenesis in a model of experimental cirrhosis produced tion of 7 days' duration to study the production of thiobarbiby CCl 4 administration. 8 From an experimental standpoint, turic acid reactive substances (TBARS), total glutathione extrahepatic biliary obstruction caused by bile duct ligature (TG), reduced glutathione (GSH), and oxidized glutathione reliably reproduces the cholestasis syndrome, 9-11 and thus (GSSG), and the enzymatic activities of GSH-peroxidase, provides an optimal model for the study of hepatoprotective GSSG-reductase, and GSH-transferase. Four groups of six rats drugs. We used this model to investigate the hepatoprotective each were treated with saline, drug solvent, S-adenosyl-L-meeffects of SAM 12 with biochemical and histopathological analthionine (SAM) 5 mg/kg/d, subcutaneously, or SAM 10 mg/kg/ yses. The present study was designed to evaluate the protecd, subcutaneously. Extrahepatic biliary obstruction increased tive effect of two doses of SAM in a model of acute cholestasis. TBARS. SAM had the dose-dependent effects of inhibitingWe measured biochemical parameters and oxidative stress, TBARS production and increasing TG content, mainly as a which was estimated as the equilibrium between oxidating result of the increase in GSH. The activity of GSH-peroxidase factors (thiobarbituric acid reactive substances and oxidized and GSH-transferase was also significantly increased. In renal glutathione [GSSG]) and antioxidant defenses (levels of retissue these effects were statistically significant only in aniduced glutathione and activity of enzymes that control glutamals given the higher dose of SAM. In liver we found a reducthione). Through transmethylation reactions, SAM restores plasma duct. For surgery the animals were anesthetized with ethyl ether membrane fluidity in hepatocytes 3 ; transsulfuration reac-and an abdominal midline incision was made. Muscle and peritoneal tions enhance the detoxicant capacity of hepatocytes by structures were dissected to expose the bile duct, which was careincreasing the amount of endogenous cysteine, glutathione, fully dissected and ligated with braided silk at two levels.13 Surgery and taurine. 2,4 in the sham-operated group was performed with the same procedure except that the bile duct was not ligated. Recent clinical and experimental studies have shown thatEach of these two groups was divided into four treatment groups treatment with SAM has important benefits in intrahepatic (n Å 6 rats per group): 1) isotonic saline solution (pH 7.4), 2) SAM cholestasis caused by liver disease associated with acute or solvent (L-lysine, pH 7.4), 3) SAM 5 mg/kg/d (Boehringer Ingelheim chronic cholestasis, pregnancy, and the use of certain drugs Españ a SA, Barcelona, Spain), and 4) SAM 10 mg/kg/d. In groups 1 and 2 we administered a volume equivalent to that used for the higher dose of SAM. In all, 48 animals were used.In all groups the route of ...

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Section: Discussionmentioning

confidence: 99%

Effects ofS-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats

et al. 1997

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“…The enzyme consists of two subunits, ␣ and ␤. Various isoforms of both subunits have been described (1)(2)(3)(4)(5). Both subunits are required for catalytic activity (6,7), which consists of the coupling of ATP hydrolysis to the active transport of Na ϩ and K ϩ ions against their electrochemical gradients across plasma membranes.…”

Section: Namentioning

confidence: 99%

“…In the hybrid ␣444/␤-gal, the ␤-galactosidase is adjacent to Ala 444 of the ␣ 1 -subunit. This amino acid is localized between the phosphorylation site Asp 346 (2,3,34) and the peptides that become labeled by the ATP analogs 8-N 3 ATP and 2-N 3 ATP and fluorescein isothiocyanate (35)(36)(37). Therefore, the fusion protein ␣444/␤-gal should also be expressed on the cytosolic side.…”

Section: Functional Expression Of ␤-Galactosidase Fusion Proteins In mentioning

confidence: 99%

Transmembrane Topology of α- and β-Subunits of Na+,K+-ATPase Derived from β-Galactosidase Fusion Proteins Expressed in Yeast

Fiedler¹,

Scheiner‐Bobis

1996

Journal of Biological Chemistry

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Various models of the transmembrane topology of the Na ؉ ,K ؉ -ATPase predict either 8 or 10 membrane spans for the ␣-subunit and one to three membrane spans for the ␤-subunit. Structure/function analysis, however, requires precise knowledge about the folding of enzymes. Therefore, the intention of this work was to establish a transmembrane topology model for the subunits of Na LGGYP 236 ) of the dog ␤-subunit. The fusion constructs were expressed in yeast cells for studies on the localization of the fused reporter enzyme. Activity measurements of the reporter enzyme revealed that only intracellular fusion sites lead to active ␤-galactosidase. Indirect immunofluorescence microscopy with cells expressing ␣ 1 /␤-galactosidase and ␤/␤-galactosidase hybrid proteins demonstrated that inactive ␤-galactosidase is associated with the yeast plasma membrane and can be detected from the extracellular side. The data obtained suggest that Pro 236 of the ␤-subunit is located on the extracellular surface, corresponding to a model with one transmembrane segment, and that the ␣-subunit of the Na ؉ ,K ؉ -ATPase consists of 10 membrane-associated spans. They also suggest that a stretch of the ␣ 1 -subunit between membrane spans M7 and M8 might be hidden within the membrane, surrounded by the other hydrophobic spans, in analogy to the P-loop of Na ؉ or K ؉ channels and to the "hourglass" structure of water channels.

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“…We observed that both drugs totally or partially 'reverted' hepatocyte and erythrocyte Na þ ,K þ -and Ca 2þ -ATPase membrane activities in CCl 4 liver damage. The ATPases, located in the plasma membrane of animal cells, maintain the characteristic intracellular concentration of ions, determine the transmembrane electrochemical gradient and influence many functions [29][30][31][32][33]. As colchiceine and UDCA were useful in the maintenance of a functional state of liver and erythrocyte membranes, they could also contribute to the improvement of the functional status in liver disease.…”

Section: Discussionmentioning

confidence: 99%

Effect of colchiceine and ursodeoxycholic acid on hepatocyte and erythrocyte membranes and liver histology in experimentally induced carbon tetrachloride cirrhosis in rats

Nava-Ocampo

Suster

Muriel

1997

Eur J Clin Investigation

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Abstract. Colchiceine and ursodeoxycholic acid (UDCA) are drugs currently in use as therapy for different types of liver damage. We evaluated their ability to reverse the damage induced by carbon tetrachloride (CCl 4 ) in rats. Six groups were analysed: (1) CCl 4 (0 . 4 g kg ¹1 , i.p., three times a week) for 13 weeks; (2) CCl 4 for 8 weeks followed by colchiceine (60 mg kg ¹1 ) + CCl 4 for 5 weeks; (3) CCl 4 for 8 weeks and thereafter UDCA (25 mg kg ¹1 ) þ CCl 4 for 5 weeks. Groups 4, 5 and 6 were appropriate controls of colchiceine, UDCA and vehicles respectively. Na þ ,K þ -and Ca 2þ -ATPase activities and the cholesterol-phospholipid (CH/PL) ratio from erythrocyte and hepatocyte membranes were quantified. Membrane enzymatic activities and CH/PL ratios were affected more in group 1 than groups 2 and 3. We concluded that colchiceine and UDCA were effective drugs in this model of liver damage.

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[1] Overview: The Na,K-pump

Cited by 237 publications

References 80 publications

Effects ofS-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats

Effects ofS-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats

Transmembrane Topology of α- and β-Subunits of Na+,K+-ATPase Derived from β-Galactosidase Fusion Proteins Expressed in Yeast

Effect of colchiceine and ursodeoxycholic acid on hepatocyte and erythrocyte membranes and liver histology in experimentally induced carbon tetrachloride cirrhosis in rats

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