Putative determinants of the cellular response to hyperthermia

Area of Science:

• Cellular Biology
• Stress Response
• Molecular Biology

Background:

• Heat shock proteins (hsp) play a role in cellular thermotolerance.
• Different heat-resistant states in Chinese hamster cells show varied recovery kinetics from heat-induced damage.
• Previous studies linked faster recovery to hsp70 expression.

Purpose of the Study:

• To investigate the recovery kinetics of heat-induced cellular perturbations in Chinese hamster cells with altered hsp27 expression and in heat-sensitive cell lines.
• To identify potential cellular markers for predicting responses to hyperthermia.

Main Methods:

• Comparison of recovery rates of protein and RNA synthesis, and hsp70 localization in hsp27-overexpressing cells versus wild-type cells.
• Analysis of recovery kinetics in permanently heat-sensitive cell lines.
• Assessment of heat-induced alterations in nuclear hsp70 association.

Main Results:

• Recovery of protein synthesis inhibition was similar between hsp27-transfected and control cells.
• Hsp27-transfected cells showed more rapid recovery from heat-induced inhibition of total RNA synthesis and increased nuclear hsp70 association.
• Heat-sensitive cell lines exhibited delayed recovery of total cellular RNA synthesis and excess nuclear hsp70 association, but not protein synthesis recovery.

Conclusions:

• The kinetics of recovery from heat-induced alterations in total cellular RNA synthesis and hsp70 localization are potential determinants of cellular response to hyperthermia.
• These recovery kinetics could form the basis for predictive assays in clinical hyperthermia treatments.