Dexamethasone enhances serum deprivation-induced necrotic death of rat C6 glioma cells through activation of glucocorticoid receptors.
Glucocorticoids have been shown to be neurotoxic and appear to play a role in neuronal cell loss during aging and following neuropathological insults. However, very little is known about the effects of these steroid hormones on glial cells. The effect of the synthetic glucocorticoid dexamethasone (DEX) on glial cell viability was therefore examined by measuring neutral red uptake into rat C6 glioma cells. Serum deprivation markedly reduced cell viability, and this effect was significantly enhanced by DEX. Electrophoretic analysis showed that the cell damage induced by either serum deprivation alone or in combination with DEX was not accompanied by the degradation of DNA into nucleosomic fragments. Electron microscopic studies confirmed that serum deprivation and glucocorticoid treatment caused necrotic cell death. Furthermore, the effect of DEX on cell viability could be mimicked by the glucocorticoid receptor agonist RU28362, and completely prevented by the glucocorticoid receptor antagonist RU38486. These results indicate that dexamethasone can enhance the necrotic death of glioma cells induced by serum deprivation, suggesting that glucocorticoids may be involved in the chronic alteration of brain function arising from neuropathological damage to glial cells.
Morita
K
K
Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. km@basic.med.tokushima-u.ac.jp
Ishimura
K
K
Tsuruo
Y
Y
Wong
D L
DL
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm / Q000302:isolation & purification; D003907:Dexamethasone / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology*; D008854:Microscopy, Electron; D009336:Necrosis; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D014407:Tumor Cells, Cultured
D000732:Androstanols; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone