In a variety of non-phagocytic cell types, there is a marked increase in intracellular levels of reactive oxygen species (ROS), including superoxide and H2O2, after ligand stimulation. We demonstrate that in NIH 3T3 cells transient expression of constitutively activated forms of the small GTP-binding proteins Ras or Rac1 leads to a significant increase in intracellular ROS. An increase in intracellular ROS is also demonstrated after growth factor [platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)] or cytokine [tumour necrosis factor-α (TNF-α) or interleukin (IL)-1β] stimulation of NIH 3T3 cells. Expression of a dominant negative allele of Rac1 inhibits the rise in ROS seen after Ras expression or after stimulation by either growth factors or cytokines. These results provide the first demonstration of the pathway by which ligand stimulation of ROS occurs in non-phagocytic cells and suggest that the family of Ras-related small GTP-binding proteins may function as regulators of the intracellular redox state.
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September 1996
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Research Article|
September 01 1996
Regulation of reactive-oxygen-species generation in fibroblasts by Rac 1
Maitrayee SUNDARESAN;
Maitrayee SUNDARESAN
*Cardiology Branch, NHLBI, NIH, 10 Center Drive, MSC1650, Building 10, Room 7B-15, Bethesda, MD 20892-1650
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Zu-Xi YU;
Zu-Xi YU
†Pathology Section, NHLBI, NIH, Bethesda, MD 20892
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Victor J FERRANS;
Victor J FERRANS
†Pathology Section, NHLBI, NIH, Bethesda, MD 20892
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David J SULCINER;
David J SULCINER
*Cardiology Branch, NHLBI, NIH, 10 Center Drive, MSC1650, Building 10, Room 7B-15, Bethesda, MD 20892-1650
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Silvio GUTKIND;
Silvio GUTKIND
‡Molecular Signaling Unit, NIDR, NIH, Bethesda, MD 20892
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Kaikobad J. IRANI;
Kaikobad J. IRANI
§Cardiology Division, Johns Hopkins School of Medicine, Baltimore, MD 21287, U.S.A.
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Pascal J. GOLDSCHMIDT-CLERMONT;
Pascal J. GOLDSCHMIDT-CLERMONT
§Cardiology Division, Johns Hopkins School of Medicine, Baltimore, MD 21287, U.S.A.
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Toren FINKEL
Toren FINKEL
‖
*Cardiology Branch, NHLBI, NIH, 10 Center Drive, MSC1650, Building 10, Room 7B-15, Bethesda, MD 20892-1650
‖To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
June 24 1996
Revision Received:
July 15 1996
Accepted:
July 16 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (2): 379–382.
Article history
Received:
June 24 1996
Revision Received:
July 15 1996
Accepted:
July 16 1996
Citation
Maitrayee SUNDARESAN, Zu-Xi YU, Victor J FERRANS, David J SULCINER, Silvio GUTKIND, Kaikobad J. IRANI, Pascal J. GOLDSCHMIDT-CLERMONT, Toren FINKEL; Regulation of reactive-oxygen-species generation in fibroblasts by Rac 1. Biochem J 1 September 1996; 318 (2): 379–382. doi: https://doi.org/10.1042/bj3180379
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