OXYGEN-FREE RADICALS AS INDUCERS OF HEAT-SHOCK PROTEIN-SYNTHESIS IN CULTURED HUMAN NEUROBLASTOMA-CELLS - RELEVANCE TO NEURODEGENERATIVE DISEASE

We studied heat shock protein (HSP) synthesis by cultured human neurob lastoma cells in response to either hyperthermia or high levels of sup eroxide anion (oxygen free radical). Both treatment modalities resulte d in induced synthesis of the same major HSP species with an additive effect on the latter and on cell growth inhibition upon combined treat ments. Exposure to superoxide anion in the presence of the free radica l scavenging enzymes, superoxide dismutase and catalase improved cell survival and prevented HSP induction. These findings suggest a common mechanism by which various forms of injury, such as hyperthermia, caus e HSP induction, that is, via oxidative stress or increased production of oxygen free radicals. Increased expression of some HSPs has been d etected in association with the pathological lesions that characterize some neurodegenerative diseases such as the neurofibrillary tangles o f Alzheimer's disease. This, in turn, suggests that chronic oxidative stress may play a role in the pathogenesis of these disorders.