A rise in intracellular calcium may mediate ischemic damage by phospho
lipid hydrolysis and proteolysis. Heat shock proteins have been shown
to provide protection from various forms of cell stress, but not from
models of Ca2+-mediated injury. The effect of heat preconditioning in
a model of ionomycin-induced injury in cultured renal tubular epitheli
al cells (BSC-1) was examined. Hsp70-mRNA expression was induced by hy
perthermia (HT) (42 degrees C, 60 min). Hsp70 protein accumulation was
maximal after 12-18 h and returned to baseline levels by 96 h. Treatm
ent of BSC-I cells with ionomycin (7.0 mu M) produced lethal cell inju
ry characterized by LDH release. Cells examined at 18 h after HT were
significantly less damaged than cells studied at 96 h after HT. Our da
ta are the first to demonstrate that heat preconditioning confers prot
ection from Ca2+-mediated cell injury. The state of increased toleranc
e is transient and closely parallels kinetics of Hsp70 expression.