Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells

被引:62
作者
Rahman, I
Bel, A
Mulier, B
Donaldson, K
MacNee, W
机构
[1] Univ Edinburgh, Royal Infirm, Dept Med, Resp Med Unit,Rayne Lab, Edinburgh EH3 9YW, Midlothian, Scotland
[2] Napier Polytech, Dept Biol Sci, Edinburgh EH10 5DT, Midlothian, Scotland
关键词
gamma-glutamylcysteine synthetase; gamma-glutamyl transpeptidase; A549; cells;
D O I
10.1152/ajplung.1998.275.1.L80
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 mu M), xanthine/xanthine oxidase (50 mu M/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0.008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O-2) resulted in a time-dependent increase in GSH levels, gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 mu M) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells.
引用
收藏
页码:L80 / L86
页数:7
相关论文
共 39 条
  • [1] [Anonymous], 1996, Methods in nitric oxide research
  • [2] ANTIINFLAMMATORY ACTIONS OF STEROIDS - MOLECULAR MECHANISMS
    BARNES, PJ
    ADCOCK, I
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1993, 14 (12) : 436 - 441
  • [3] REDOX AND ADDITION CHEMISTRY OF QUINOID COMPOUNDS AND ITS BIOLOGICAL IMPLICATIONS
    BRUNMARK, A
    CADENAS, E
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1989, 7 (04) : 435 - 477
  • [4] NORMAL ALVEOLAR EPITHELIAL LINING FLUID CONTAINS HIGH-LEVELS OF GLUTATHIONE
    CANTIN, AM
    NORTH, SL
    HUBBARD, RC
    CRYSTAL, RG
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1987, 63 (01) : 152 - 157
  • [5] EXPRESSION OF MULTIPLE GAMMA-GLUTAMYL-TRANSFERASE GENES IN MAN
    COURTAY, C
    HEISTERKAMP, N
    SIEST, G
    GROFFEN, J
    [J]. BIOCHEMICAL JOURNAL, 1994, 297 : 503 - 508
  • [6] CUTO R, 1989, VIB SPECTROSC, V86, P6377
  • [7] TISSUE-SPECIFIC EXPRESSION OF MULTIPLE GAMMA-GLUTAMYL TRANSPEPTIDASE MESSENGER-RNAS IN RAT EPITHELIA
    DARBOUY, M
    CHOBERT, MN
    LAHUNA, O
    OKAMOTO, T
    BONVALET, JP
    FARMAN, N
    LAPERCHE, Y
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (06): : C1130 - C1137
  • [8] EXTRACELLULAR GLUTATHIONE IS A SOURCE OF CYSTEINE FOR CELLS THAT EXPRESS GAMMA-GLUTAMYL-TRANSPEPTIDASE
    HANIGAN, MH
    RICKETTS, WA
    [J]. BIOCHEMISTRY, 1993, 32 (24) : 6302 - 6306
  • [9] Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells
    Hatcher, EL
    Alexander, JM
    Kang, YJ
    [J]. BIOCHEMICAL PHARMACOLOGY, 1997, 53 (05) : 747 - 754
  • [10] INDUCTION OF INTRACELLULAR GLUTATHIONE IN ALVEOLAR TYPE-II PNEUMOCYTES FOLLOWING BCNU EXPOSURE
    JENKINSON, SG
    LAWRENCE, RA
    ZAMORA, CA
    DENEKE, SM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (02): : L125 - L130