Related Experiment Videos
Group I metabotropic receptors down-regulate nitric oxide induced caspase-3 activity in rat hippocampal neurons
1Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA. kmaiese@med.wayne.edu
Abstract:
Invoking the modulation of parallel cellular pathways, the G-protein metabotropic glutamate receptors (mGluRs) and nitric oxide (NO) have been shown to require a host of signal transduction pathways to modulate neuronal programmed cell death (PCD). Since the cysteine protease caspase-3 (CPP32) is one of the principal mediators of PCD in several nonneuronal cell systems, we investigated whether CPP32 activity was linked to both NO induced PCD and mGluR neuroprotection. We demonstrate that NO directly increases the activity of CPP32 by approximately 400% over a 6 h period that is necessary, at least in part, for the generation of neuronal PCD. Activation of only Group I mGluRs completely ameliorates the induction of CPP32 activity by NO and prevents the induction of PCD.