title: N-acetylcysteine-promoted survival of PC12 cells is glutathione-independent but transcription-dependent.
abstract: Our prior work established that comparable concentrations of N-acetylcysteine (NAC) both block the proliferation of PC12 cells and prevent death of trophic factor-deprived sympathetic neurons and PC12 cells. The present work addresses several aspects of the mechanisms of these actions. NAC increases intracellular levels of glutathione (GSH) by approximately 10-fold in PC12 cells. However, blockade of this increase by treatment with buthionine sulfoximine did not affect either promotion of survival or inhibition of DNA synthesis. Thus, these actions of NAC are independent of its effects on intracellular GSH. NAC's actions in our system do not appear to be dependent on its anti-oxidant/radical scavenger properties, but may be due to its activity as a reductant. Consistent with this, several other reducing agents, the most effective of which was 2,3-dimercaptopropanol, mimicked NAC in blocking DNA synthesis and suppressing death of PC12 cells and sympathetic neurons. Finally, we observed that in striking contrast to nerve growth factor and a number of other trophic agents, the survival-promoting effects of NAC on PC12 cells are blocked by actinomycin D. This suggests that NAC may act by inducing specific gene expression.
authors.affiliation: Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Yan
authors.forename: G
authors.initials: G
authors.lastname: Ferrari
authors.forename: L A
authors.initials: LA
authors.lastname: Greene
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004112:Dimercaprol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D010084:Oxidation-Reduction; D016716:PC12 Cells; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004112:Dimercaprol; D004247:DNA; D005978:Glutathione; D000111:Acetylcysteine