Effect of diphenyl diselenide, diphenyl ditelluride and ebselen on cerebral Na+, K+-ATPase activity in rats

被引：105

作者：

Borges, VC ^{[1
]}

Rocha, JBT ^{[1
]}

Nogueira, CW ^{[1
]}

机构：

[1] Univ Fed Santa Maria, Ctr Ciencias Nat & Exatas, Dept Quim, BR-97105900 Santa Maria, RS, Brazil

来源：

TOXICOLOGY | 2005年 / 215卷 / 03期

关键词：

Na+; K+-ATPase; organoselenium; organotellurium; ebselen; toxicity;

D O I：

10.1016/j.tox.2005.07.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In the present study, we investigated the in vitro effect of diphenyl ditelluride, diphenyl diselenide and ebselen on Na+, K-ATPase activity of rat brain. The results demonstrated that all compounds significantly inhibited (in the mu M range) Na+, K+-ATPase activity. Diphenyl ditelluride, at low concentrations, provoked an increase in Na+, K+-ATPase activity. Dithiothreitol (DTT), at 3 mM, protected the inhibition caused by diphenyl ditelluride, diphenyl diselenide and ebselen in Na+, K+-ATPase activity. Post-incubation of diphenyl diselenide-treated homogenate with DTT completely recovered enzyme activity. DTT was able to recover the enzyme inhibition induced by 20 mu M of diphenyl ditelluride, but was partially able to recover inhibition induced by high concentrations of organotellurium compound. Conversely, DTT did not recover ebselen-induced Na+, K+-ATPase inhibition. The mechanism of inhibition by diphenyl diselenide, diphenyl ditelluride and ebselen in Na+, K+-ATPase activity revealed: decreased maximal velocity and Km. Cerebral Na+, K+-ATPase is a potential molecular target for the toxic effect of organochalcogens and the inhibition may occur through a change in the crucial thiol groups of this enzyme. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：191 / 197

页数：7

共 46 条

[1] MERCURY BLOCKS NA-K-ATPASE BY A LIGAND-DEPENDENT AND REVERSIBLE MECHANISM [J].

ANNER, BM ;

MOOSMAYER, M ;

IMESCH, E .

AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 262 (05) :F830-F836

[2] Effect of organic forms of selenium on δ-aminolevulinate dehydratase from liver, kidney, and brain of adult rats [J].

Barbosa, NBV ;

Rocha, JBT ;

Zeni, G ;

Emanuelli, T ;

Beque, MC ;

Braga, AL .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 1998, 149 (02) :243-253

[3] DO DEFECTS IN MITOCHONDRIAL ENERGY-METABOLISM UNDERLIE THE PATHOLOGY OF NEURODEGENERATIVE DISEASES [J].

BEAL, MF ;

HYMAN, BT ;

KOROSHETZ, W .

TRENDS IN NEUROSCIENCES, 1993, 16 (04) :125-131

[4]

Bertorello AM, 1995, NEWS PHYSIOL SCI, V10, P253

[5] Selenite incubated with NADPH and mammalian thioredoxin reductase yields selenide, which inhibits lipoxygenase and changes the electron spin resonance spectrum of the active site iron [J].

Bjornstedt, M ;

Odlander, B ;

Kuprin, S ;

Claesson, HE ;

Holmgren, A .

BIOCHEMISTRY, 1996, 35 (26) :8511-8516

[6] Inhibition of ATPase activity in rat synaptic plasma membranes by simultaneous exposure to metals [J].

Carfagna, MA ;

Ponsler, GD ;

Muhoberac, BB .

CHEMICO-BIOLOGICAL INTERACTIONS, 1996, 100 (01) :53-65

[7] Ebselen as a peroxynitrite scavenger in vitro and ex vivo [J].

Daiber, A ;

Zou, MH ;

Bachschmid, M ;

Ullrich, V .

BIOCHEMICAL PHARMACOLOGY, 2000, 59 (02) :153-160

[8] FUNCTION AND CONTROL OF NA-K-ATPASE IN SINGLE NEPHRON SEGMENTS OF THE MAMMALIAN KIDNEY [J].

DOUCET, A .

KIDNEY INTERNATIONAL, 1988, 34 (06) :749-760

[9] EXPEDIENT SYNTHESIS OF EBSELEN AND RELATED-COMPOUNDS [J].

ENGMAN, L ;

HALLBERG, A .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (12) :2964-2966

[10]

FAIRHILL LT, 1969, IND TOXICOLOGY, P120

← 1 2 3 4 5 →