Stege G J, Brunsting J F, Kampinga H H, Konings A W
Department of Radiobiology, University of Groningen, The Netherlands.
J Cell Physiol. 1995 Sep;164(3):579-86. doi: 10.1002/jcp.1041640316.
Heat-induced nuclear protein aggregation and subsequent disaggregation were measured in nonpreheated and preheated (thermotolerant) HeLa S3 cells. The effect of thermotolerance on the formation of and recovery from heat-induced nuclear protein aggregates was related to the cellular levels of hsp27, hsp60, hsp70, hsc70, and hsp90. Cells heated at different time points after the thermotolerance trigger showed various levels of protection against heat-induced nuclear protein aggregation. This protection, however, did not parallel the development and decay of thermotolerance on cell survival. The protection was maximal when the thermotolerance level already had started to decay. The level of protection against nuclear protein aggregation did however parallel the cellular level of hsp70 indicating that hsp70 may be involved in this process. At all stages during the development and decay, thermotolerant cells showed a more rapid recovery (disaggregation) from the heat-induced nuclear protein aggregates than non-thermotolerant cells. The rates of disaggregation during development and decay of thermotolerance paralleled the cellular levels of hsp27 suggesting that hsp27 is somehow involved in this recovery process from heat-induced nuclear protein aggregates. The total cellular levels of none of the individual hsp's completely correlate with development and decay of thermotolerance, indicating that overexpression of any of these hsp's alone does not determine the level of thermotolerance. Clonogenic cell survival paralleled the rates of disaggregation, leading to the notion that recovery processes are the most important determinant for the thermotolerant state of HeLa S3 cells. The best correlation with clonogenic survival was found when both initial aggregation and subsequent disaggregation were taken into account, suggesting that the combined action of various hsp's in these two processes have to be included in thermotolerance development and decay.
在未预热和预热（耐热）的HeLa S3细胞中测量了热诱导的核蛋白聚集及随后的解聚情况。耐热性对热诱导核蛋白聚集体形成和恢复的影响与hsp27、hsp60、hsp70、hsc70和hsp90的细胞水平有关。在耐热性触发后的不同时间点加热的细胞，对热诱导核蛋白聚集表现出不同程度的保护作用。然而，这种保护作用与耐热性对细胞存活的发展和衰退并不平行。当耐热性水平已经开始衰退时，保护作用达到最大。对核蛋白聚集的保护水平与hsp70的细胞水平平行，表明hsp70可能参与了这一过程。在发展和衰退的所有阶段，耐热细胞比不耐热细胞从热诱导核蛋白聚集体中恢复（解聚）得更快。耐热性发展和衰退过程中的解聚速率与hsp27的细胞水平平行，表明hsp27在某种程度上参与了从热诱导核蛋白聚集体的恢复过程。单个hsp的总细胞水平均与耐热性的发展和衰退不完全相关，这表明单独过表达这些hsp中的任何一种都不能决定耐热性水平。克隆形成细胞存活率与解聚速率平行，这表明恢复过程是HeLa S3细胞耐热状态的最重要决定因素。当同时考虑初始聚集和随后的解聚时，与克隆形成存活率的相关性最好，这表明在耐热性的发展和衰退过程中，必须考虑各种hsp在这两个过程中的联合作用。
