ROLE OF THE CELLULAR STRESS-RESPONSE IN THE BIOGENESIS OF CYSTEAMINE-INDUCED ASTROCYTIC INCLUSIONS IN PRIMARY CULTURE

Cysteamine (CSH; 2-mercaptoethylamine) stimulates the accumulation of peroxidase-positive inclusions in cultured astroglia akin to those obs erved in the aging periventricular brain. Because CSH induces the synt hesis of a stress protein (heme oxygenase) in rat liver, we hypothesiz ed that aspects of the cellular stress response may play a role in the biogenesis of CSH-induced astrocyte granules. In the present study, w e performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astro cyte cultures to CSH enhanced immunostaining for heme oxygenase-1 (HO- 1) and heat-shock proteins 27, 72, and 90, but not glucose-regulated p rotein 94, relative to untreated cultures. CSH-pretreated astrocytes e xhibited enhanced tolerance to H2O2 toxicity relative to untreated cel ls, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known indu cer of the stress response, elicited astrocyte granulation similar to that observed with CSH. Chronic induction of HO-1 and other stress pro teins may participate in the biogenesis of metalloporphyrin-rich inclu sions in CSH-treated astroglial cultures and in astrocytes of the agin g periventricular brain.