The mechanism whereby heat shock induces apoptosis depends on the innate sensitivity of cells to stress |
| |
Authors: | Kerstin Bellmann Steve J Charette Philippe J Nadeau Dominic J Poirier Anne Loranger Jacques Landry |
| |
Institution: | 1.Centre de recherche en cancérologie de l’Université Laval,L’H?tel-Dieu de Québec,Québec,Canada;2.Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (H?pital Laval),Québec,Canada |
| |
Abstract: | The cellular response to heat shock (HS) is a paradigm for many human diseases collectively known as “protein conformation
diseases” in which the accumulation of misfolded proteins induces cell death. Here, we analyzed how cells having a different
apoptotic threshold die subsequent to a treatment with HS. Cells with a low apoptotic threshold mainly induced apoptosis through
activation of conventional stress kinase signaling pathways. By contrast, cells with a high apoptotic threshold also died
by apoptosis but likely after the accumulation of heat-aggregated proteins as revealed by the formation of aggresomes in these
cells, which were associated with the generation of atypical nuclear deformations. Inhibition of the proteasome or expression
of an aggregation prone protein produced similar nuclear alterations. Furthermore, elevated levels of chaperones markedly
suppressed both HS-induced nuclear deformations and apoptosis induced upon protein aggregation whereas they had little effect
on stress kinase-mediated apoptosis. We conclude that the relative contribution of stress signaling pathways and the accumulation
of protein aggregates to cell death by apoptosis is related to the innate sensitivity of cells to deadly insults. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|