Hyperthermia and protein aggregation : role of heat shock proteins

Hyperthermia (treatment of cells a few degrees above their growth temperature) can lead to cell kill (reproductive capacity), and can also enhance the sensitivity of cells for radiation and chemotherapeutics. Enhancement of the radiosensitivity by heat is of clinical importance. Combined treatments of heat and radiation are already practiced in a number of radiotherapeutic institutes. The mechanisms underlying the process of cell killing by heat and of heat radiosensitization are unclear as yet. Data from the literature indicate an important role for heat-induced protein denaturation and aggregation in hyperthermic cell killing. It has already been shown that thermotolerance (transient resistance induced by a pretreatment) at the survival level paralleled resistance at the level of protein denaturation/aggregation. So, protection against protein denaturation/aggregation may result in protection against heat killing. Cells exposed to heat (or other forms of stress) respond by synthesizing a specific set of proteins, the so called “heat shock proteins (hsp’s)” or “stress proteins”. These proteins are thought to be involved in protection against damage induced by heat (stress). The purpose of the experiments described in this thesis was to obtain more insight into the protective mechanism(s) of heat shock proteins in protein denaturation and aggregation.