EFFECT OF ANISOTONIC CELL-VOLUME MODULATION ON GLUTATHIONE-S-CONJUGATE RELEASE, T-BUTYLHYDROPEROXIDE METABOLISM AND THE PENTOSE-PHOSPHATE SHUNT IN PERFUSED-RAT-LIVER

被引:68
作者
SAHA, N
STOLL, B
LANG, F
HAUSSINGER, D
机构
[1] UNIV FREIBURG, MED KLIN, HUGSTETTERSTR 55, W-7800 FREIBURG, GERMANY
[2] UNIV INNSBRUCK, INST PHYSIOL, A-6020 INNSBRUCK, AUSTRIA
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1992年 / 209卷 / 01期
关键词
D O I
10.1111/j.1432-1033.1992.tb17307.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
1. Addition of 1-chloro-2,4-dinitrobenzene to isolated perfused rat liver results in the rapid formation of its glutathione-S-conjugate [S-(2,4-dinitrophenyl)glutathione], which is released into both, bile and effluent perfusate. Anisotonic perfusion did not affect total S-conjugate formation, but release of the S-conjugate into the perfusate was increased (decreased) following hypertonic (hypotonic) exposure at the expense of excretion into bile. Stimulation of S-conjugate release into the perfusate following hypertonic exposure paralleled the time course of volume-regulatory net K+ uptake. 2. Basal steady-state release of oxidized glutathione (GSSG) into bile was 1.30 +/- 0.12 nmol . g-1 . min-1 (n = 18) during normotonic (305 mOsmol/l) perfusion and was 3.8 +/- 0.3 nmol . g-1 . min-1 in the presence of 1-butylhydroperoxide (50 mumol/l). Hypotonic exposure (225 mOsmol/1) lowered both, basal and t-butylhydroperoxide(50 mumol/l)-stimulated GSSG release into bile by 35% and 20%, respectively, whereas hypertonic exposure (385 mOsmol/l) increased. Anisotonic exposure was without effect on t-butylhydroperoxide removal by the liver. GSSG release into bile also decreased by 33% upon liver-cell swelling due to addition of glutamine plus glycine (2 mmol/l, each). 3. Hypotonic exposure led to a persistent stimulation (CO2)-C-14 production from [1-C-14]glucose by about 80%, whereas (CO2)-C-14 production from [6-C-14]glucose increased by only 10%. Conversely, hypertonic exposure inhibited (CO2)-C-14 production from [1-C-14]glucose by about 40%, whereas (CO2)-C-14 production from [6-C-14]glucose was unaffected. The effect of anisotonicity on (CO2)-C-14 production from [1-C-14]glucose was also observed in presence of 1-butylhydroperoxide (50 mumol/1), which increased (CO2)-C-14 production from [1-C-14]glucose by about 40%. 4. t-Butylhydroperoxide (50 pmol/1) was without significant effect on volume-regulatory K+ fluxes following exposure to hypotonic (225 mOsmol/l) or hypertonic (385 mOsmol/l) perfusate. Lactate dehydrogenase release from perfused rat liver under the influence of t-butylhydroperoxide was increased by hypertonic exposure compared to hypotonic perfusions. 5. The data suggest that hypotonic cell swelling stimulates flux through the pentose-phosphate pathway and diminishes loss of GSSG under conditions of mild oxidative stress. Hypotonically swollen cells are less prone to hydroperoxide-induced lactate dehydrogenase release than hypertonically shrunken cells. Hypertonic cell shrinkage stimulates the excretion of glutathione-S-conjugates into the sinusoidal circulation at the expense of biliary secretion.
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页码:437 / 444
页数:8
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