N-ACETYLCYSTEINE (D-STEREOISOMERS AND L-STEREOISOMERS) PREVENTS APOPTOTIC DEATH OF NEURONAL CELLS

In the present study we tested whether N-acetyl-L-cysteine (LNAC) affe cts apoptotic death of neuronal cells caused by trophic factor depriva tion. LNAC, an antioxidant, elevates intracellular levels of glutathio ne. 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 m aintains long-term survival in the absence of other trophic support, U nlike NGF, LNAC does not induce or maintain neurite outgrowth or somat ic 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 ineffe ctive in this regard, Since it has been hypothesized that trophic fact ors prevent neuronal death by either preventing or coordinating cell c ycle progression, we tested whether LNAC or DNAC treatment can affect cell cycle, We found that both (but not other antioxidants) suppress p roliferation and DNA synthesis by PC12 cells and do so at concentratio ns similar to those at which they prevent apoptotic death, Although th e abilities of LNAC and DNAC to rescue cells from apoptosis triggered by trophic factor deprivation could derive from their direct influence s on cellular responsiveness to oxidative stress, our observations rai se the possibility of a mechanism involving cell cycle regulation.