Suppression of nerve growth factor-induced neuronal differentiation of PC12 cells. N-acetylcysteine uncouples the signal transduction from ras to the mitogen-activated protein kinase cascade.

The Journal of Biological Chemistry
Hideaki KamataHajime Hirata

Abstract

The cellular redox state is thought to play an important role in a wide variety cellular signaling pathways. Here, we investigated the involvement of redox regulation in the nerve growth factor (NGF) signaling pathway and neuronal differentiation in PC12 cells. N-acetyl-L-cysteine (NAC), which acts as a reductant in cells both by its direct reducing activity and by increasing the synthesis of the cellular antioxidant glutathione, inhibited neuronal differentiation induced by NGF or by the expression of oncogenic ras in PC12 cells. NAC suppressed NGF-induced c-fos gene expression and AP-1 activation. These results suggest that neuronal differentiation and NGF signaling are subject to regulation by the cellular redox state. NAC also suppressed the NGF-induced activation of mitogen-activated protein kinases (MAPKs) and decreased the amount of tyrosine phosphorylation of MAPKs. The suppression of MAPK by NAC was independent of glutathione synthesis. In parallel with the suppression of MAPK, the activation of MAPK kinase kinase activity was also suppressed in the presence of NAC. In contrast, NGF-induced activation of Ras was not inhibited by NAC. The inhibitory effect of NAC on the MAPK cascade was independent of transcription and ...Continue Reading

References

Dec 1, 1992·Neurology·P JennerC D Marsden
May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M B Toledano, W J Leonard
Dec 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·G W StuartR D Palmiter
Dec 8, 1995·The Journal of Biological Chemistry·T RussoE Appella
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·M T AndersonL A Herzenberg
Aug 31, 1995·Nature·H R Bourne
Sep 8, 1995·The Journal of Biological Chemistry·H M LanderA Novogrodsky
Mar 1, 1995·Trends in Biochemical Sciences·E Cano, L C Mahadevan
Jun 23, 1995·The Journal of Biological Chemistry·M H Cobb, E J Goldsmith
Jan 1, 1994·Methods in Enzymology·P Moldéus, I A Cotgreave
Nov 1, 1994·Trends in Biochemical Sciences·G DaumU R Rapp
Feb 24, 1995·Cell·D Thanos, T Maniatis
Nov 1, 1993·Journal of Neurochemistry·Z Pan, R Perez-Polo
Nov 1, 1994·Molecular and Cellular Biology·S A MoodieA Wolfman
Jul 1, 1994·Trends in Biochemical Sciences·J AvruchJ M Kyriakis
Sep 2, 1994·Science·C A Lange-Carter, G L Johnson
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·H SchenkK Schulze-Osthoff
Jun 1, 1994·Journal of Neurochemistry·D SampathJ R Perez-Polo
Apr 1, 1993·Trends in Biochemical Sciences·E Nishida, Y Gotoh

❮ Previous
Next ❯

Citations

Jun 4, 1999·Progress in Biophysics and Molecular Biology·M H Cobb
Jan 16, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·L CanesiG Gallo
Mar 4, 2000·Free Radical Biology & Medicine·R G Allen, M Tresini
Apr 17, 1999·Cellular Signalling·H Kamata, H Hirata
Apr 30, 1998·Current Opinion in Cell Biology·T Finkel
Apr 1, 2008·The Journal of Biological Chemistry·Rayudu GopalakrishnaThomas H McNeill
Aug 22, 2009·Cardiovascular Research·Tsung-Ming LeeNen-Chung Chang
Mar 3, 2011·BMC Molecular Biology·Muriel E de BoerDick Roelofs
Nov 22, 2001·Biochemical and Biophysical Research Communications·M FukunagaU Kikkawa
Dec 17, 2008·Neurological Research·Andrew M HartMikael Wiberg
Jan 15, 2014·Journal of Physiology and Biochemistry·Monika SobczakLudmila Zylinska
Jun 28, 2011·The Bulletin of Tokyo Dental College·Kensuke SaitoKan-Ichi Nakagawa
Oct 30, 2003·Journal of Cellular Physiology·Lina MusallamMarc Bilodeau
Jun 21, 2005·Annals of the New York Academy of Sciences·Liang-Yo YangChwen-Ming Shih
Jul 26, 2005·British Journal of Plastic Surgery·C-G ZhangA M Hart
Apr 18, 2012·Clinical Science·Tsung-Ming LeeNen-Chung Chang
Feb 21, 2014·Colloids and Surfaces. B, Biointerfaces·Min DengJianwen Gu
Sep 7, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Sukhdeep Kaur Sahambi, Barbara F Hales

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.