Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1.

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.

• 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)

Chemical References

• Amino Acids
• Caspase Inhibitors
• Spectrin
• L-Lactate Dehydrogenase
• Cathepsins
• Calpain
• Caspase 3

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