TY - JOUR T1 - Potassium Deprivation-Induced Apoptosis of Cerebellar Granule Neurons: A Sequential Requirement for New mRNA and Protein Synthesis, ICE-Like Protease Activity, and Reactive Oxygen Species JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4696 LP - 4706 DO - 10.1523/JNEUROSCI.16-15-04696.1996 VL - 16 IS - 15 AU - Jörg B. Schulz AU - Michael Weller AU - Thomas Klockgether Y1 - 1996/08/01 UR - http://www.jneurosci.org/content/16/15/4696.abstract N2 - Potassium (K+) deprivation-induced apoptosis of cerebellar granule neurons requires new mRNA and protein synthesis. Using a fluorogenic substrate for interleukin-1β converting enzyme (ICE), we show that K+ deprivation of cerebellar granule neurons induces cycloheximide-sensitive ICE-like protease activity. A peptide inhibitor of ICE-like protease activity, Ac-YVAD-chloromethylketone (Ac-YVAD-CMK), prevents K+ deprivation-induced apoptosis. Further, reactive oxygen species (ROS) are essential mediators of K+ deprivation-induced apoptosis of cerebellar granule neurons because neuronal death is also blocked by superoxide dismutase, N-acetyl-l-cysteine, and free radical spin traps. Using fluorescent assays, we show that ROS production after K+ deprivation is blocked by actinomycin D, cycloheximide, and Ac-YVAD-CMK, suggesting that ROS act downstream of gene transcription, mRNA translation, and ICE activation. Taken together, we show that new mRNA and protein synthesis, activation of ICE-like proteases, and ROS production are sequential events in K+ deprivation-induced apoptosis of cerebellar granule neurons. ER -