Spontaneous apoptosis and expression of cell surface heatshock proteins incultured EL-4 lymphoma cells

The expression of heat-shock proteins (HSPs) is enhanced in stressed cells and can protect cells from stress-induced injury. However, existing data ab out the relationship between apoptosis and HSP expression is contradictory. In this paper, a mouse lymphoma cell death model system is used to detect simultaneously both the process of apoptosis and the level of HSP expressio n. The model was established after discovering that spontaneous apoptosis a nd spontaneous cell surface HSP expression occurs in EL-4 mouse lymphoma ce lls during normal optimal culture conditions. The data show that apoptotic EL-4 cells had higher levels of hsp25, hsp60, hsp70 and hsp90 exposed on th e plasma membrane surface than viable cells. The level of surface HSPs was found to increase through several stages of early and late apoptotic death as measured by flow cytometry, with the highest levels observed during the loss of cell membrane phospholipid asymmetry. Heat shock and actinomycin D significantly increased the proportion of apoptotic cells in culture. Howev er, hyperthermia only stimulated a weak and temporary increase in surface H SP expression, whereas actinomycin D strongly elevated the level of surface and intracellular HSPs, particularly in live cells. These results show an associative relationship between apoptosis and HSP expression.-The relation ship between the progression of cell death and HSP expression suggests a ro le for membrane HSP expression in programmed cell death.