Expression of Herpes Simplex Virus Type 2 Protein ICP10 PK Rescues Neurons from Apoptosis Due to Serum Deprivation or Genetic Defects

Previous studies have shown that the herpes simplex virus type 2 protein kinase ICP10 PK activates the Ras/MEK/MAPK pathway in nonneuronal cells. Here we report that ectopically expressed ICP10 PK has anti-apoptotic activity in various paradigms of neuronal cell death. Neuronally differentiated PC12...

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Bibliographic Details
Published in:Experimental neurology 2002-03, Vol.174 (1), p.118-122
Main Authors: Perkins, Dana, Yu, Yanxing, Bambrick, Linda L., Yarowsky, Paul J., Aurelian, Laure
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - drug effects
Biological and medical sciences
Blood Proteins - pharmacology
Cell Count
Cell Survival - drug effects
Cells, Cultured
Development. Senescence. Regeneration. Transplantation
Enzyme Activation - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression
herpes simplex
hippocampal neurons
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - metabolism
ICP10
Mice
Mutation
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
PC12
PC12 Cells
Protein-Serine-Threonine Kinases - biosynthesis
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - pharmacology
Rats
Ribonucleotide Reductases - biosynthesis
Ribonucleotide Reductases - genetics
Ribonucleotide Reductases - pharmacology
Transfection
Trisomy
Ts16
Vertebrates: nervous system and sense organs
Viral Proteins - biosynthesis
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Summary:Previous studies have shown that the herpes simplex virus type 2 protein kinase ICP10 PK activates the Ras/MEK/MAPK pathway in nonneuronal cells. Here we report that ectopically expressed ICP10 PK has anti-apoptotic activity in various paradigms of neuronal cell death. Neuronally differentiated PC12 cells and primary murine hippocampal cultures transfected with an expression vector for ICP10 PK were protected from cell death resulting from growth factor withdrawal. Protection from apoptosis was also seen in ICP10 PK-transfected hippocampal neurons from the trisomy 16 mouse, a naturally occuring genetic abnormality the human analog of which is Down syndrome. Cells transfected with an expression vector for a mutant that lacks kinase activity were not protected, although it was expressed as well as ICP10 PK. The data indicate that ICP10 PK has a broad anti-apoptotic activity in neuronal cells which depends on a functional PK.
ISSN:0014-4886
1090-2430
DOI:10.1006/exnr.2001.7849