Expression of the 70 kDa heat shock protein (HSP70) induced by a first insult is associated with protection from a subsequent ischemic insult in brain. Expression of the human inducible HSP70 was previously shown to protect astrocytes in primary culture from combined oxygen-glucose deprivation. These studies have now been extended to demonstrate that HSP70 expression also protects from isolated glucose deprivation. Slight protection was seen against hydrogen peroxide (H2O2) exposure. Glutathione levels decrease less after glucose deprivation or H2O2 exposure (200 microM) in the cells overexpressing HSP70, compared to either beta-galactosidase expressing or uninfected controls (P < 0.01). These data suggest that the HSP70-expressing cells suffered less oxidative stress since their glutathione levels were better preserved.