Role of the Cellular Stress Response in the Biogenesis of Cysteamine-Induced Astrocytic Inclusions in Primary Culture
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 61, Issue 5, pages 1755–1765, November 1993
How to Cite
Mydlarski, M. B., Liang, J.-J. and Schipper, H. M. (1993), Role of the Cellular Stress Response in the Biogenesis of Cysteamine-Induced Astrocytic Inclusions in Primary Culture. Journal of Neurochemistry, 61: 1755–1765. doi: 10.1111/j.1471-4159.1993.tb09813.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Recieved November 9, 1992; revised March 1, 1993; accepted March 15, 1993.
- eme oxygenase;
- eat-shock protein;
- lucose-regulated protei;
- eroxidase activity
Abstract— Cysteamine (CSH; 2-mercaptoethylamine) stimulates the accumulation of peroxidase-positive inclusions in cultured astroglia akin to those observed in the aging periventricular brain. Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of the cellular stress response may play a role in the biogenesis of CSH-induced astro-cyte granules. In the present study, we performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astrocyte cultures to CSH enhanced immunostaining for heme oxygenase-1 (HO-1) and heat-shock proteins 27, 72, and 90, but not glucose-regulated protein 94, relative to untreated cultures. CSH-pretreated astrocytes exhibited enhanced tolerance to H2O2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known inducer of the stress response, elicited astrocyte granulation similar to that observed with CSH. Chronic induction of HO-1 and other stress proteins may participate in the biogenesis of metal-loporphyrin-rich inclusions in CSH-treated astroglial cultures and in astrocytes of the aging periventricular brain.