Effect of phosphotyrosine phosphatase over‐expression on glutathione metabolism in normal and oncogene‐transformed cells

FEBS Letters

Vincenzini, Maria Teresa¹  Rigacci, Stefania¹  Ramponi, Giampietro¹  Ruggiero, Marco²  Iantomasi, Teresa¹  Marraccini, Patrizia¹  Pacini, Stefania² 

[1] Dipartimento di Scienze Biochimiche Universita di Firenze, viale Morgagni 50, 50134 Firenze, Italy;Istituto di Patologia Generale, Università di Firenze, vials Morgagni 50, 50134 Firenze, Italy

关键词: Glutathione;    Oncogene;    Phosphatase;    Neoplasia;    GSH;    reduced glutathione;    GSSG;    oxidized glutathione;    GST;    glutathione-S-transferase (EC 5.1.18);    GR;    glutathione reductase (EC 1.6.4.2);    γ-GCS;    γ-glutamyl cysteine synthetase (EC 6.3.2.2);   

DOI  :  10.1016/0014-5793(94)00377-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We measured the level of reduced glutathione (GSH) and oxidized glutathione (GSSG) in normal and oncogene-transformed NIH/3T3 fibroblasts and 32D hematopoietic cells. NIH/3T3 cells transformed by the activated oncogenes erbB, src, and raf, showed increased levels of GSH with concomitant alterations in the levels of GSH-related enzymes. Transfection and over-expression of a synthetic gene coding for a phosphotyrosine protein phosphatase (PTPase), which inhibited the proliferation of normal and transformed NIH/3T3 cells, was accompanied by a decrease in GSH levels in normal and erbB-transformed fibroblasts, and by an increase in src and raf transformants. Among GSH-related enzymes, only γ-glutamylcysteine synthetase was altered in normal and erbB-transformed NIH/3T3 fibroblasts following PTPase transfection. Therefore, tyrosine phosphorylation could be selectively involved in the regulation of GSH metabolism in normal and oncogene-transformed NIH/3T3 fibroblasts, possibly by a dual-type effect on receptor/oncoprotein-mediated mitogenic signal transduction. However, no relationship was observed between the GSH and PTPase effect on cell growth, either after oncogene transfection or PTPase transfection. Moreover, the changes in GSH metabolism were specifically related to cell lineage. In fact GSH and related enzymes did not change in 32D hematopoietic cells transformed by the same activated erbB oncogene and in those - normal or transformed over-expressing the PTPase: in these cells also, over-expression of the PTPase gene was not accompanied by growth inhibition.

【 授权许可】

Unknown