D1 dopamine receptor mediates dopamine-induced cytotoxicity via the ERK signal cascade.

The Journal of Biological Chemistry
Jun ChenAnita Sidhu

Abstract

Postsynaptic striatal neurodegeneration occurs through unknown mechanisms, but it is linked to high extracellular levels of synaptic dopamine. Dopamine-mediated cytotoxicity of striatal neurons occurs through two distinct pathways: autoxidation and the D1 dopamine receptor-linked signaling pathway. Here we investigated the mitogen-activated protein kinase (MAPK) signaling pathways activated upon the acute stimulation of D1 dopamine receptors. In SK-N-MC neuroblastoma cells, endogenously expressing D1 dopamine receptors, dopamine caused activation of phosphorylated (p-)ERK1/2 and of the stress-signaling kinases, p-JNK and p-p38 MAPK, in a time- and dose-dependent manner. Selective stimulation of D1 receptors with the agonist SKF R-38393 caused p-ERK1/2, but not p-JNK or p-p38 MAPK activation, in a manner sensitive to the receptor-selective antagonist SCH 23390, protein kinase A inhibition (KT5720), and MEK1/2 inhibition (U0126 or PD98059). Activation of ERK by D1 dopamine receptors resulted in oxidative stress and cytotoxicity. In cells transfected with a catalytically defective mutant of MEK1, the upstream ERK-specific kinase, both dopamine- and SKF R-38393-mediated cytotoxicity was markedly attenuated, confirming the participa...Continue Reading

References

Mar 1, 1992·Molecular and Cellular Biology·R H ChenJ Blenis
Jan 30, 1990·Biochemical and Biophysical Research Communications·A Sidhu, P H Fishman
Nov 24, 1995·Science·Z XiaM E Greenberg
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·A A ReszkaE H Fischer
Jun 23, 1995·The Journal of Biological Chemistry·M H Cobb, E J Goldsmith
May 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G R Post, J H Brown
Oct 4, 1996·The Journal of Biological Chemistry·J D English, J D Sweatt
Jan 1, 1996·Annual Review of Neuroscience·R A Segal, M E Greenberg
Oct 6, 1997·Cellular Signalling·A PaulR Plevin
Dec 24, 1998·Nuclear Medicine and Biology·P Hantraye
Apr 10, 1999·Nature Neuroscience·C M AtkinsJ D Sweatt
Oct 16, 1999·The Journal of Biological Chemistry·H RubinfeldR Seger
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·A AlessandriniJ V Bonventre
Jun 1, 2000·Movement Disorders : Official Journal of the Movement Disorder Society·I GhorayebF Tison
Sep 2, 2000·The Journal of Biological Chemistry·M KarandikarM H Cobb
Sep 9, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·A Sidhu, H B Niznik
Mar 15, 2001·Current Opinion in Cell Biology·W E Miller, R J Lefkowitz
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·S NamuraA Alessandrini
Nov 13, 2001·Developmental Cell·E FormstecherH Chneiweiss
Jan 24, 2002·Molecular Cell·John M Schmitt, Philip J S Stork

❮ Previous
Next ❯

Citations

Nov 30, 2010·Invertebrate Neuroscience : in·Chloe Burman, Peter D Evans
Dec 1, 2006·Apoptosis : an International Journal on Programmed Cell Death·Anthony S L ChanYung H Wong
Oct 29, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nikhil M UrsMarc G Caron
Mar 14, 2007·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Manon LebelMichel Cyr
Oct 20, 2015·Journal of Cellular Physiology·Taehyung LeeNarayanan Parameswaran
Nov 26, 2011·Neurobiology of Disease·S Ares-SantosR Moratalla
Oct 13, 2015·Progress in Neurobiology·Rosario MoratallaMicaela Morelli
Jun 11, 2005·Immunology·Elizabeth J MeredithJohn Gordon
Aug 4, 2009·Journal of Neurochemistry·Chloe BurmanPeter D Evans
May 6, 2009·British Journal of Pharmacology·Carla FerradaRafael Franco
Feb 10, 2009·The European Journal of Neuroscience·Jun ChenAnita Sidhu
Apr 23, 2013·Journal of Internal Medicine·S Ares-SantosR Moratalla
Jan 31, 2006·Trends in Neurosciences·Yuri Bozzi, Emiliana Borrelli
Mar 6, 2016·The Journal of Pharmacology and Experimental Therapeutics·Jenni KononoffPertti Panula
Oct 6, 2010·Biochimica Et Biophysica Acta·Deanne J MitchellRodney F Minchin
May 5, 2012·The International Journal of Biochemistry & Cell Biology·Evandro Fei FangTzi Bun Ng
Oct 5, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sampath RamachandiranGary W Miller
Apr 20, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Christopher D HerzogJeffrey H Kordower
Sep 27, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Christopher S Wilcox

❮ 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.