Dexamethasone inhibits apoptosis in C6 glioma cells through increased expression of Bcl-XL.
The glucocorticoid dexamethasone (Dex) has been reported to modulate a number of signaling pathways and physiological processes, including apoptosis. This study was carried out to investigate the cytoprotective mechanism of Dex in C6 glioma cells. Pre-treatment of cells with Dex inhibited apoptosis induced by staurosporine, etoposide and thapsigargin. Apoptosis inhibition correlated with blockade of mitochondrial cytochrome c release, abolition of caspase-3 activity along with inhibition of caspase-9 and PARP cleavage. Dex-mediated cytoprotection coincided with the induction of the anti-apoptotic protein, Bcl-X(L). The specific glucocorticoid receptor antagonist, RU486, reversed the anti-apoptotic effect of Dex and prevented Bcl-X(L) induction. Here, we show for the first time that knockdown of Bcl-X(L) expression with siRNA reversed the protective effects of the glucocorticoid in glioma cells. We conclude that Dex-mediated inhibition of apoptosis in C6 glioma cells is through induction of Bcl-X(L).
Ní Chonghaile
Tríona
T
Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Concannon
Caoimhín G
CG
Szegezdi
Eva
E
Gorman
Adrienne M
AM
Samali
Afshin
A
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; C494813:Bcl2l1 protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D051020:bcl-X Protein; D015735:Mifepristone; D019284:Thapsigargin; D005047:Etoposide; D003907:Dexamethasone; D045304:Cytochromes c; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine