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Journal of Neuroscience, Vol 15, 2857-2866, Copyright © 1995 by Society for Neuroscience
N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal cells
G Ferrari, CY Yan and LA Greene
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
In the present study we tested whether N-acetyl-L-cysteine (LNAC) affects
apoptotic death of neuronal cells caused by trophic factor deprivation.
LNAC, an antioxidant, elevates intracellular levels of glutathione. We used
serum-deprived PC12 cells, neuronally differentiated PC12 cells deprived of
serum and NGF, and NGF-deprived neonatal sympathetic neurons. In each case
LNAC prevents apoptotic DNA fragmentation and maintains long-term survival
in the absence of other trophic support. Unlike NGF, LNAC does not induce
or maintain neurite outgrowth or somatic hypertrophy. To rule out actions
of LNAC metabolic derivatives, we assessed N-acetyl-D-cysteine (DNAC). DNAC
also prevents death of PC12 cells and sympathetic neurons. However, other
antioxidants were ineffective in this regard. Since it has been
hypothesized that trophic factors prevent neuronal death by either
preventing or coordinating cell cycle progression, we tested whether LNAC
or DNAC treatment can affect cell cycle. We found that both (but not other
antioxidants) suppress proliferation and DNA synthesis by PC12 cells and do
so at concentrations similar to those at which they prevent apoptotic
death. Although the abilities of LNAC and DNAC to rescue cells from
apoptosis triggered by trophic factor deprivation could derive from their
direct influences on cellular responsiveness to oxidative stress, our
observations raise the possibility of a mechanism involving cell cycle
regulation.
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