Cascade of caspase activation in potassium-deprived cerebellar granule neurons: targets for treatment with peptide and protein inhibitors of apoptosis

Molecular and Cellular Neurosciences
E GerhardtJ B Schulz

Abstract

Cerebellar granule neurons (CGN) cultured in the presence of serum and depolarizing potassium concentrations undergo apoptosis when switched to serum-free medium containing physiological potassium concentrations. Here we show that processing of the key protease, caspase-3, depends on the activation of caspase-9, but not of caspase-8. Selective peptide inhibitors of caspase-9 block processing of caspase-3 and caspase-8 and inhibit apoptosis, whereas a selective inhibitor of caspase-8 blocks neither processing of caspase-3 nor cell death. The data obtained with peptide inhibitors were confirmed by adenovirally mediated ectopic expression of the cytokine response modifier A (crmA), the baculovirus protein p35, and the X chromosome-linked inhibitor of apoptosis (XIAP). Further, caspase-8-activating death receptors do not mediate apoptosis in CGN and potassium withdrawal-induced apoptosis evolves unaltered in gld or lpr mice, which harbor mutations in the CD95/CD95 ligand system. Thus, neuronal apoptosis triggered by potassium deprivation is death receptor-independent but involves the mitochondrial pathway of caspase activation.

References

Aug 1, 1994·Molecular and Cellular Biology·R J Clem, L K Miller
Feb 11, 1994·Science·V GagliardiniJ Yuan
Apr 1, 1993·Journal of Virology·N E CrookL K Miller
Nov 1, 1996·DNA and Cell Biology·M R DigbyJ W Lowenthal
Mar 21, 1997·The Journal of Biological Chemistry·Q ZhouG S Salvesen
Mar 1, 1997·Cancer Immunology, Immunotherapy : CII·W RothM Weller
Jul 17, 1997·Nature·Q L DeverauxJ C Reed
Jul 1, 1997·The European Journal of Neuroscience·M LeistP Nicotera
Sep 28, 1998·Biochimica Et Biophysica Acta·H R Stennicke, G S Salvesen
Nov 26, 1998·The Journal of Biological Chemistry·M Garcia-CalvoN A Thornberry
Dec 5, 1998·Biochemical and Biophysical Research Communications·C ParkS Yonehara
Apr 22, 1999·Annals of Neurology·J B SchulzM A Moskowitz
May 26, 1999·Current Biology : CB·J TschoppK Hofmann
Jul 1, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G A WannerW Ertel

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Citations

May 1, 2002·The Journal of Cell Biology·Girish V PutchaEugene M Johnson
Jan 15, 2003·Journal of Neuroscience Research·Andrea Caballero-Benítez, Julio Morán
Jun 7, 2011·Neuroscience Letters·Zhongmin YuanYongjian Lu
May 19, 2009·European Journal of Cell Biology·Johanne Wirenfeldt AsmussenVladimir Berezin
Jun 12, 2009·Journal français d'ophtalmologie·G MichelO Naoun
Mar 25, 2005·The European Journal of Neuroscience·Xavier XifroJosé Rodríguez-Alvarez
Apr 11, 2009·Journal of Neuroscience Research·Alicia Guemez-Gamboa, Julio Morán
Jun 29, 2007·Journal of Neurochemistry·Alfredo MiñanoJosé Rodríguez-Alvarez
Mar 4, 2008·Journal of Neuroscience Research·Alfredo MiñanoJosé Rodríguez-Alvarez
Dec 24, 2010·Clinical & Experimental Ophthalmology·Frank SchuettaufSebastian Thaler
Aug 18, 2004·Biochemical Pharmacology·Caroline RouauxAnne-Laurence Boutillier
Jul 31, 2012·Neurobiology of Disease·Maj N EnevoldsenElisabeth Bock
Jan 8, 2015·Frontiers in Neurology·Paulina Carriba, Joan X Comella
Jun 14, 2005·Biochemical Pharmacology·Elvira G JordàAntoni Camins
May 16, 2007·Apoptosis : an International Journal on Programmed Cell Death·Antonella BobbaErsilia Marra
Apr 26, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Guodong CaoJun Chen
Mar 3, 2004·Journal of Neuroscience Research·Jin ZhongWei-Hua Lee
Oct 21, 2017·Archives of Toxicology·Marcel LeistJan G Hengstler
Sep 15, 2004·Cell and Tissue Research·Jörg B Schulz, Björn H Falkenburger
Dec 8, 2004·Retina·Richard S B NewsomZdenek J Gregor
Jan 8, 2005·Cell Death and Differentiation·T A PrechtK A Heidenreich
Dec 11, 2013·Translational Stroke Research·Niyathi Hegde Shah, Elias Aizenman
Jun 11, 2009·Communicative & Integrative Biology·P CalissanoG Amadoro
Nov 6, 2003·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Rosalba AmodioEnnio Esposito
Jul 9, 2003·Annals of the New York Academy of Sciences·Kim A Heidenreich

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