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Role of the Cellular Stress Response in the Biogenesis of Cysteamine‐Induced Astrocytic Inclusions in Primary Culture
Author(s) -
Mydlarski Marc B.,
Liang JinJun,
Schipper Hyman M.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb09813.x
Subject(s) - cysteamine , biogenesis , neuroscience , microbiology and biotechnology , chemistry , biology , biochemistry , gene
— 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 H 2 O 2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H 2 O 2 , 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.