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

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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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Author information

Authors and Affiliations

  1. Center for Traumatic Brain Injury Studies, Department of Neuroscience, McKnight Brain Institute of the University of Florida, Gainesville, Florida

    Shankar Sadasivan, Anu Waghray, Stephen F. Larner, Ronald L. Hayes & Kevin K. W. Wang

  2. Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, McKnight Brain Institute of the University of Florida, 100 S. Newell Drive, Box 100256, Gainesville, FL, 32610, USA

    Ronald L. Hayes & Kevin K. W. Wang

  3. Department of Biochemistry and Molecular Biology, University of Maryland, Rockville, Maryland

    Anu Waghray

  4. Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida

    William A. Dunn Jr.

Authors
  1. Shankar Sadasivan
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  2. Anu Waghray
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  3. Stephen F. Larner
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  4. William A. Dunn Jr.
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  5. Ronald L. Hayes
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  6. Kevin K. W. Wang
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Corresponding author

Correspondence to Kevin K. W. Wang.

Additional information

Shankar Sadasivan and Anu Waghray have contributed equally to this work.

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Sadasivan, S., Waghray, A., Larner, S.F. et al. Amino acid starvation induced autophagic cell death in PC-12 cells: Evidence for activation of caspase-3 but not calpain-1. Apoptosis 11, 1573–1582 (2006). https://doi.org/10.1007/s10495-006-7690-6

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  • DOI: https://doi.org/10.1007/s10495-006-7690-6

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