In:
Journal of Neuroscience Research, Wiley, Vol. 66, No. 6 ( 2001-12-15), p. 1074-1082
Abstract:
Etoposide‐induced death comprises such nuclear events as the formation of topoisomerase II‐DNA cleavable complex and cytosolic events including caspase activation. By first establishing the temporospatial death sequence triggered by etoposide in a neuronal cell line, MN9D overexpressing Bcl‐X L (MN9D/Bcl‐X L ) or control vector (MN9D/Neo), we examined whether formation of this complex is primarily responsible for cell death and at which strategic points and how Bcl‐X L blocks etoposide‐induced neuronal death. Etoposide induced death that was dependent on caspase, cycloheximide, and calpain in MN9D/Neo cells. Etoposide also induced death in enucleated MN9D/Neo cells, although this was less severe. The level of topoisomerase II‐DNA cleavable complex reached at a maximum of 2 hr after etoposide treatment was identical in MN9D/Neo and MN9D/Bcl‐X L cells. In MN9D/Neo cells, cytochrome c release into the cytosol and caspase activation occurred as early as 2 hr and 3–6 hr after etoposide treatment, respectively. Etoposide‐induced DNA laddering potentially via caspase appeared as early as 12 hr after drug treatment, followed by nuclear swelling in MN9D/Neo cells ( 〉 18–20 hr). Subsequently, nuclear condensation started by 24–28 hr and became apparent thereafter. All of these events except for nuclear swelling were substantially blocked in MN9D/Bcl‐X L . At the later stage of cell death ( 〈 32–36 hr), a specific cleavage of Bax and fodrin appeared that was completely blocked by calpain inhibitor or by Bcl‐X L . Taken together, our data suggest that Bcl‐X L prevents etoposide‐induced neuronal death by exerting its anticaspase and anticalpain effect on cellular events after the formation of topoisomerase II‐DNA cleavable complex that may not be a major contributor to cell death. J Neurosci. Res. 66:1074–1082, 2001. © 2001 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0360-4012
,
1097-4547
Language:
English
Publisher:
Wiley
Publication Date:
2001
detail.hit.zdb_id:
1474904-X
SSG:
12
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