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The relationship is investigated between superoxide levels in single cultured rat cerebellar granule neurons exposed continuously to glutamate in low KCl medium and the deregulation of cytoplasmic Ca2+. Cells that maintain a regulated cytoplasmic-free Ca2+ and mitochondrial polarization in the presence of glutamate show no increase in superoxide levels(More)
Decreases in GSH pools detected during ischemia sensitize neurons to excitotoxic damage. Thermodynamic analysis predicts that partial GSH depletion will cause an oxidative shift in the thiol redox potential. To investigate the acute bioenergetic consequences, neurons were exposed to monochlorobimane (mBCl), which depletes GSH by forming a fluorescent(More)
The pathologic activation of NMDA receptors by glutamate is a major contributor to neuronal cell death after stroke. Receptor activation causes a massive influx of calcium into the neuron that is accumulated by the mitochondria. The favored hypothesis is that the calcium loaded mitochondria generate reactive oxygen species that damage and ultimately killed(More)
During the use of tetrapeptide and other proprietary caspase inhibitors in the study of neurodegeneration, we had concluded that mechanisms other than the inhibition of caspases contributed to the protective effects of certain caspase inhibitors. Here we report our studies to identify a target for and hence a mechanism by which the tetrapeptide inhibitor(More)
The mitochondrion has moved to the center stage in the drama of the life and death of the neuron. The mitochondrial membrane potential controls the ability of the organelle to generate ATP, generate reactive oxygen species and sequester Ca(2+) entering the cell. Each of these processes interact, and their deconvolution is far from trivial. The cultured(More)
Although glial cells have been traditionally viewed as supportive partners of neurons, studies of the last 20 years demonstrate that astrocytes possess functional receptors for neurotransmitters and other signaling molecules and respond to their stimulation via release of chemical transmitters (called gliotransmitters) such as glutamate, ATP, and d-serine.(More)
Programmed cell death (pcd) may take the form of apoptosis or of nonapoptotic pcd. Whereas cysteine aspartyl-specific proteases (caspases) mediate apoptosis, the mediators of nonapoptotic cell death programs are much less well characterized. Here we report that alternative, nonapoptotic pcd induced by the neurokinin-1 receptor (NK(1)R) activated by its(More)
The relationship is investigated between mitochondrial membrane potential (Delta Psi(M)), respiration and cytochrome c (cyt c) release in single neural bcl-2 transfected cells (GT1-7bcl-2) or GT1-7puro cells during apoptosis induced by staurosporine (STS). Bcl-2 inhibited the mitochondrial release of cyt c and apoptosis. Three different cell responses to(More)
Several receptors that mediate apoptosis have been identified, such as Fas and tumor necrosis factor receptor I. Studies of the signal transduction pathways utilized by these receptors have played an important role in the understanding of apoptosis. Here we report the first ligand-receptor pair-the neuropeptide substance P and its receptor, neurokinin-1(More)
Barbiturates are widely used as anesthetics, anticonvulsants, and neuroprotective agents. However, barbiturates may also inhibit mitochondrial respiration, and mitochondrial inhibitors are known to potentiate NMDA receptor-mediated neurotoxicity. Here we used rat cortical cultures to examine the effect of barbiturates on neuronal mitochondria and responses(More)
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