INDUCTION OF INTRACELLULAR GLUTATHIONE IN ALVEOLAR TYPE-II PNEUMOCYTES FOLLOWING BCNU EXPOSURE

被引:19
作者
JENKINSON, SG [1 ]
LAWRENCE, RA [1 ]
ZAMORA, CA [1 ]
DENEKE, SM [1 ]
机构
[1] UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1994年 / 266卷 / 02期
关键词
N; N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA; CYSTINE TRANSPORT; OXYGEN TOXICITY;
D O I
10.1152/ajplung.1994.266.2.L125
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) is a potent inhibitor of glutathione reductase (GSSG-Red) activity in both tissues and cells. We examined the effects of treating alveolar type II cells with BCNU and found that a marked decrease in cellular GSSG-Red activity occurred in these cells associated with a time-dependent increase in cellular glutathione (GSH) concentrations. The increase in GSH was not found to be related to changes in cellular gamma-glutamyl transpeptidase activity, gamma-glutamylcysteine synthetase activity, nor increased intracellular transport of cystine. When the BCNU-exposed cells were incubated with hydrogen peroxide to produce oxidant stress, the cells exhibited increased susceptibility to oxidant damage when compared with controls, despite the fact that cellular concentrations of GSH were markedly elevated.
引用
收藏
页码:L125 / L130
页数:6
相关论文
共 41 条
[1]  
Akerboom T P, 1981, Methods Enzymol, V77, P373
[2]   INACTIVATION OF GLUTATHIONE REDUCTASE BY 2-CHLOROETHYL NITROSOUREA-DERIVED ISOCYANATES [J].
BABSON, JR ;
REED, DJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1978, 83 (02) :754-762
[3]   INDUCTION OF CYSTINE TRANSPORT ACTIVITY IN ISOLATED RAT HEPATOCYTES BY SULFOBROMOPHTHALEIN AND OTHER ELECTROPHILIC AGENTS [J].
BANNAI, S ;
TAKADA, A ;
KASUGA, H ;
TATEISHI, N .
HEPATOLOGY, 1986, 6 (06) :1361-1368
[4]  
BANNAI S, 1989, J BIOL CHEM, V264, P18480
[5]  
BANNAI S, 1984, J BIOL CHEM, V259, P2435
[6]  
BANNAI S, 1984, NATURE, V311, P308
[7]   TRANSPORT OF CYSTINE AND CYSTEINE AND CELL-GROWTH IN CULTURED HUMAN-DIPLOID FIBROBLASTS - EFFECT OF GLUTAMATE AND HOMOCYSTEATE [J].
BANNAI, S ;
ISHII, T .
JOURNAL OF CELLULAR PHYSIOLOGY, 1982, 112 (02) :265-272
[8]   ADAPTIVE ENHANCEMENT OF CYSTINE AND GLUTAMATE UPTAKE IN HUMAN-DIPLOID FIBROBLASTS IN CULTURE [J].
BANNAI, S ;
KITAMURA, E .
BIOCHIMICA ET BIOPHYSICA ACTA, 1982, 721 (01) :1-10
[9]   INVIVO STUDIES ON THE TARGET TISSUE METABOLISM, COVALENT BINDING, GLUTATHIONE DEPLETION, AND TOXICITY OF 4-IPOMEANOL IN BIRDS, SPECIES DEFICIENT IN PULMONARY ENZYMES FOR METABOLIC-ACTIVATION [J].
BUCKPITT, AR ;
STATHAM, CN ;
BOYD, MR .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1982, 65 (01) :38-52
[10]  
CRAPO JD, 1978, LAB INVEST, V39, P640