Raising intracellular calcium attenuates neuronal apoptosis triggered by staurosporine or oxygen-glucose deprivation in the presence of glutamate receptor blockade.
The relationship between intracellular Ca(2+) ([Ca(2+)](i)) regulation and programmed cell death is not well-defined; both increases and decreases in [Ca(2+)](i) have been observed in cells undergoing apoptosis. We determined [Ca(2+)](i) in cultured murine cortical neurons undergoing apoptosis after exposure to staurosporine or following oxygen-glucose deprivation in the presence of glutamate receptor antagonists. Neuronal [Ca(2+)](i) was decreased 1-4 h after exposure to staurosporine (30 nM). A [Ca(2+)](i) decrease was also observed 1 h after the end of the oxygen-glucose deprivation period when MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were added to the bathing medium during the deprivation period. A similar decrease in [Ca(2+)](i) produced by reducing extracellular Ca(2+) or chelating intracellular Ca(2+) was sufficient to induce neuronal apoptosis. Raising [Ca(2+)](i) either by activating voltage-sensitive Ca(2+) channels with (-) Bay K8644 or by application of low concentrations of kainate attenuated both staurosporine and oxygen-glucose deprivation-induced apoptosis.
Canzoniero
Lorella M T
LM
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Babcock
Debra J
DJ
Gottron
Frank J
FJ
Grabb
Margaret C
MC
Manzerra
Pat
P
Snider
B Joy
BJ
Choi
Dennis W
DW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007424:Intracellular Fluid / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D019311:Staurosporine; D005947:Glucose; D010100:Oxygen; D002118:Calcium