Abstract |
Krabbe's disease ( globoid cell leukodystrophy) is a progressive cerebral degenerative disease of infancy characterized by severe myelin loss and the presence of globoid bodies in the white matter. Previous studies have suggested that psychosine is the causative agent for the pathogenesis of Krabbe's disease. In the present study, we investigated psychosine-induced injury and cell death of oligodendrocytes in enriched cultures of oligodendrocytes prepared from 3-week-old rat brain. The psychosine concentration sufficient to induce 50% cell death in oligodendrocytes was 30 micrograms/ml in the medium containing serum and 10 micrograms/ml in the serum-free medium. When oligodendrocytes were exposed to psychosine in the presence of phorbol esters, insulin, insulin-like growth factor I ( IGF-I), demethylsulfoxide, or serum albumin, the survival of oligodendrocytes was greatly increased. These results indicate that psychosine cytotoxicity against oligodendrocytes is blocked by phorbol esters, insulin, and IGF-I through activation of protein kinase-C, by dimethylsulfoxide through activation of beta-galactosidase, and by albumin through its binding to psychosine.
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Authors | K H Cho, M W Kim, S U Kim |
Journal | Developmental neuroscience
(Dev Neurosci)
Vol. 19
Issue 4
Pg. 321-7
( 1997)
ISSN: 0378-5866 [Print] Switzerland |
PMID | 9215877
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Albumins
- Hypoglycemic Agents
- Insulin
- Neuroprotective Agents
- Phorbol Esters
- Psychosine
- Insulin-Like Growth Factor I
- Dimethyl Sulfoxide
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Topics |
- Albumins
(pharmacology)
- Animals
- Brain
(pathology)
- Cell Survival
(drug effects)
- Cells, Cultured
- Dimethyl Sulfoxide
(pharmacology)
- Hypoglycemic Agents
(pharmacology)
- Insulin
(pharmacology)
- Insulin-Like Growth Factor I
(pharmacology)
- Leukodystrophy, Globoid Cell
(pathology)
- Neuroprotective Agents
(pharmacology)
- Oligodendroglia
(drug effects)
- Phorbol Esters
(pharmacology)
- Psychosine
(antagonists & inhibitors, toxicity)
- Rats
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