PMID: 9632307Jun 19, 1998Paper

Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures

Journal of Neuroscience Research
B R PikeR L Hayes

Abstract

Caspase 3-like proteases are key executioners in mammalian apoptosis, and the calpain family of cysteine proteases has also been implicated as an effector of the apoptotic cascade. However, the influence of upstream events on calpain/caspase activation and the role of calpain/caspase activation on subsequent downstream events are poorly understood. This investigation examined the temporal profile of apoptosis-related events after staurosporine-induced apoptosis in mixed glial-neuronal septo-hippocampal cell cultures. Following 3 hr exposure to staurosporine (0.5 microM), calpain and caspase 3-like proteases processed alpha-spectrin to their signature proteolytic fragments prior to endonuclease-mediated DNA fragmentation (not evident until 6 hr), indicating that endonuclease activation is downstream from calpain/caspase activation. Cycloheximide, a general protein synthesis inhibitor, completely prevented processing of alpha-spectrin by calpains and caspase 3-like proteases, DNA fragmentation and cell death, indicating that de novo protein synthesis is an upstream event necessary for activation of calpains and caspase 3-like proteases. Calpain inhibitor II and the pan-caspase inhibitor Z-D-DCB each inhibited their respective pro...Continue Reading

Citations

May 7, 1999·Environmental Health Perspectives·G E Kass, S Orrenius
Jan 11, 2013·Cell Death & Disease·T C JacksonP M Kochanek
Jun 5, 2001·Clinical Chemistry and Laboratory Medicine : CCLM·J E SpringerY Jin
Jun 15, 2004·Brain Pathology·Jose A PinedaRonald L Hayes
Jan 19, 2006·Journal of Neurochemistry·Robert D Staszewski, Bryan K Yamamoto
Oct 27, 2005·Journal of Biochemistry and Molecular Biology·Joe E Springer
Jan 13, 2000·Trends in Neurosciences·K K Wang
Dec 23, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Brian R PikeRonald L Hayes
Nov 6, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Susan M KnoblachAlan I Faden
Mar 21, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·X ZhaoR L Hayes
Nov 10, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·J K Newcomb-FernandezR L Hayes
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Jun 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H SawadaS Shimohama
Jan 28, 2005·Cellular and Molecular Neurobiology·Ying JinJoe E Springer

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