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Journal of Neuroscience, Vol 11, 2552-2563, Copyright © 1991 by Society for Neuroscience
Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription-independent mechanisms
A Rukenstein, RE Rydel and LA Greene
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Past studies revealed that NGF and fibroblast growth factor (FGF) prevent
the death of PC 12 pheochromocytoma cells that otherwise occurs in
serum-free medium. Additional agents were tested here for their abilities
to promote long-term survival of naive and NGF-pretreated (primed) PC 12
cells in serum-free conditions. Forskolin and permeant cAMP analogs
effectively prevented serum-free cell death, as did micromolar levels of
insulin and 10-100-nM levels of insulin-like growth factors I and II. In
contrast to NGF and FGF, none of these agents caused neuronal
differentiation of naive cells or neurite regeneration by primed cells.
Each of the agents also prevented rapid cell death in a balanced salt
solution, thus apparently ruling out a mechanism dependent on regulation of
nutrient uptake. Epidermal growth factor and elevated K+ appeared to slow
the rate of cell death, but did not promote long-term survival; phorbol
ester, dexamethasone, or vanadate did not prevent cell death. Each of the
survival-promoting agents was effective even when macromolecular synthesis
was blocked. Because the synthesis inhibitors themselves did not
significantly prevent cell death, such findings indicate that survival was
promoted by mechanisms that do not require synthesis of RNA or protein. In
addition, various lines of experimental evidence (using the kinase
inhibitor K-252a or PC 12 cell variants deficient either in protein kinase
A activity or in responsiveness to NGF) further suggested that the
effective agents maintain survival by independent initial pathways.
Regulation of protein kinase activity appears to be a common feature of
each pathway and may therefore play a key convergent role in mediating
prevention of cell death.
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S. R. D'Mello, K. Borodezt, and S. P. Soltoff
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D. S. Park, E. J. Morris, L. A. Greene, and H. M. Geller
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L. Stefanis, D. S. Park, C. Y. I. Yan, S. E. Farinelli, C. M. Troy, M. L. Shelanski, and L. A. Greene
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D. S. Park, L. Stefanis, C. Y. I. Yan, S. E. Farinelli, and L. A. Greene
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