Reversible changes in the nuclear lamina induced by hyperthermia.
The nuclear matrix (NM) has been identified as a potential target for heat-induced cell killing. Previous studies have shown that heat-shock may significantly modulate lamin B content. Since changes in NM structure have often been accompanied by changes in protein composition, we investigated whether hyperthermia induced changes in nuclear lamina (NL) structure in non-tolerant and thermotolerant cells, and the implications of these changes on cell survival. Using indirect immunofluorescence techniques and confocal microscopy, we found that heating cells at 42 or 45.5 degrees C caused invaginations and other distortions of the peripheral NL. While hyperthermia did not alter the number or structure of internal lamin B foci, heat-induced alterations to the peripheral NL were dose-dependent. Interestingly, NL structure recovered with time after heating in cells that were destined to live or die. Thermotolerant cells heated at 45.5 degrees C showed similar initial changes in the NL compared to non-tolerant cells, but recovery occurred much faster. Taken together, these results suggest that the amount of initial damage to the peripheral NL is not correlated with heat-induced cell killing. However, the possibility that an increased rate of recovery might confer a survival advantage cannot be discounted.
Falloon
Elizabeth A
EA
Department of Radiation Oncology, Indiana University School of Medicine, Indiana Cancer Pavilion, RT 041, 535 Barnhill Drive, Indianapolis, Indiana 46202, USA.
Dynlacht
Joseph R
JR
D016923:Cell Death; D048429:Cell Size; D002470:Cell Survival; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D034881:Nuclear Lamina / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D009687:Nuclear Proteins