Abstract |
While the apoptotic and necrotic cell death pathways have been well studied, there lacks a comprehensive understanding of the molecular events involving autophagic cell death. We examined the potential roles of the apoptosis-linked caspase-3 and the necrosis/apoptosis-linked calpain-1 after autophagy induction under prolonged amino acid (AA) starvation conditions in PC-12 cells. Autophagy induction was observed as early as three hours following amino acid withdrawal. Cell death, measured by lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays occurred within 24 h following starvation and was accompanied by an upregulation in caspase-3 activity but not calpain-1. The cell death that occurred following AA starvation was significantly alleviated by treatment with the autophagy inhibitor 3-methyl adenine but not with the broad spectrum caspase inhibitors. Thus, this study demonstrates that 3-methyladenine-sensitive autophagic cell death due to AA starvation in PC-12 cells is mechanistically and biochemically similar to, yet distinct from, classic caspase dependent apoptosis.
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Authors | Shankar Sadasivan, Anu Waghray, Stephen F Larner, William A Dunn Jr, Ronald L Hayes, Kevin K W Wang |
Journal | Apoptosis : an international journal on programmed cell death
(Apoptosis)
Vol. 11
Issue 9
Pg. 1573-82
(Sep 2006)
ISSN: 1360-8185 [Print] Netherlands |
PMID | 16703260
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Amino Acids
- Caspase Inhibitors
- Spectrin
- L-Lactate Dehydrogenase
- Cathepsins
- Calpain
- Caspase 3
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Topics |
- Amino Acids
(metabolism)
- Animals
- Autophagy
(physiology)
- Calpain
(antagonists & inhibitors, metabolism)
- Caspase 3
(metabolism)
- Caspase Inhibitors
- Cathepsins
(metabolism)
- Cell Nucleus
(ultrastructure)
- L-Lactate Dehydrogenase
(metabolism)
- Rats
- Spectrin
(metabolism)
- Starvation
(metabolism)
- Time
- Tumor Cells, Cultured
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