PMID: 11325450Apr 28, 2001Paper

Ionizing radiation affects 26s proteasome function and associated molecular responses, even at low doses

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
F Pajonk, W H McBride

Abstract

Ionizing radiation is known to activate certain signal transduction pathways, the regulation of which could involve post-transcriptional as well as transcriptional mechanisms. One of the most important post-transcriptional pathways in eukaryotic cells is the ATP- and ubiquitin-dependent degradation of proteins by the 26s proteasome. This process controls initiation of many cellular stress responses, as well as inflammatory responses under control of the transcription factor NF-kappaB. The literature on the relationship between radiation and inflammation seems somewhat paradoxical. At high doses, radiation is generally pro-inflammatory. On the other hand, low dose radiation has a long history of use in the treatment of inflammatory disease. This suggests the involvement of multiple mechanisms that may operate differentially at different dose levels. In this paper, the ability of different doses of ionizing radiation to directly affect 26s proteasome activity was tested in ECV 304 cells. Proteasome activity, IkappaBalpha protein levels, and NF-kappaB activation were monitored. Inhibition of chymotrypsin-like 20s and 26s proteasome activity was observed immediately after low- and high-dose irradiation either of cells or purified p...Continue Reading

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