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Redox state changes in density-dependent regulation of proliferation
D E Hutter1, B G Till, J J Greene
1Department of Biology, Catholic University of America, Washington, DC 20064, USA.
Experimental Cell Research
|May 1, 1997
Summary
Cellular redox state influences gene transcription and proliferation. Manipulating glutathione levels altered redox potential and fibroblast proliferation, suggesting a link between redox balance and growth control.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Transcription factor DNA binding is sensitive to cellular redox environment.
- Cellular redox state may regulate genes controlling cell proliferation.
Purpose of the Study:
- To investigate the relationship between cellular redox state and cell proliferation.
- To assess if changes in redox state correlate with contact inhibition of proliferation.
Main Methods:
- Measured levels of oxidized (GSSG) and reduced (GSH) glutathione in normal fibroblasts and fibrosarcoma cells at varying densities.
- Calculated redox potentials from glutathione levels.
- Treated subconfluent fibroblasts with glutathione synthesis modulators (buthionine sulfoximine and GSH precursors).
Main Results:
- Normal proliferating fibroblasts exhibited a more reducing redox potential (-34 mV) compared to contact-inhibited cells.
- Fibrosarcoma cells, lacking contact inhibition, did not show redox state modulation with density.
- Inhibition of GSH synthesis reduced proliferation, while GSH precursors increased proliferation.
Conclusions:
- Cellular redox state is closely linked to growth control mechanisms like contact inhibition.
- Modulation of glutathione levels impacts both cellular redox state and proliferation.
- Findings suggest redox balance plays a crucial role in regulating cell growth.