Gene transfer of calbindin D28k cDNA via herpes simplex virus amplicon vector decreases cytoplasmic calcium ion response and enhances neuronal survival following glutamatergic challenge but not following cyanide.
Excitatory amino acid overstimulation of neurons can lead to a marked rise in cytoplasmic Ca2+ concentration ([Ca2+])i) and be followed by neuron death from hours to days later. If the rise in [Ca2+]i is prevented, either by removing Ca2+ from the extracellular environment or by placing Ca2+ chelators in the cytosol of the stimulated cells, the neurotoxicity associated with excitotoxins can be ameliorated. We have recently shown that neurons infected with a herpes simplex virus amplicon vector expressing cDNA for calbindin D28k responded to hypoglycemia with decreased [Ca2+]i and increased survival relative to controls. We now report that vector-infected neurons respond to glutamatergic insults with lower [Ca2+]i than controls and with increased survival. Infected neurons exposed to sodium cyanide did not respond with lower [Ca2+]i than controls, nor did they demonstrate increased survival postinsult. We examine these results in light of our earlier report and in the context of the potential of vectors like this for neuronal gene therapy.
Department of Biological Sciences, Stanford University, California 94305-5020, USA.
T J
TJ
Meier
D Y
DY
Ho
T S
TS
Park
R M
RM
Sapolsky
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics*; D005470:Fluorometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics; D012966:Sodium Cyanide / Q000494:pharmacology
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D018076:DNA, Complementary; D064030:S100 Calcium Binding Protein G; D018698:Glutamic Acid; D016202:N-Methylaspartate; D012966:Sodium Cyanide; D007608:Kainic Acid; D002118:Calcium