Oxidative stress alters the regulatory control of p66Shc and Akt in PINK1 deficient cells

Biochemical and Biophysical Research Communications
Mary C MajBrian H Robinson

Abstract

Mitochondrial dysfunction is involved in the underlying pathology of Parkinson's Disease (PD). PINK1 deficiency, which gives rise to familial early-onset PD, is associated with this dysfunction as well as increased oxidative stress. We have established primary fibroblast cell lines from two patients with PD who carry mutations in the PINK1 gene. The phosphorylation of Akt is abrogated in the presence of oxidative stressors in the complete absence of PINK1 suggesting enhanced apoptotic signalling. We have found an imbalance between the production of reactive oxygen species where the capacity of the cell to remove these toxins by anti-oxidative enzymes is greatly reduced. The expression levels of the anti-oxidant enzymes glutathione peroxidase-1, MnSOD, peroxiredoxin-3 and thioredoxin-2 were diminished. The p66(Shc) adaptor protein has recently been identified to become activated by oxidative stress by phosphorylation at residue Ser36 which then translocates to the mitochondrial inner membrane space. The phosphorylation of p66(Shc) at Ser36 is significantly increased in PINK1 deficient cell lines under normal tissue culture conditions, further still in the presence of compounds which elicit oxidative stress. The stable transfecti...Continue Reading

References

May 1, 1981·The Journal of Clinical Investigation·K F SheuM F Utter
Mar 16, 1995·European Journal of Pharmacology·Y Y Glinka, M B Youdim
Dec 1, 1996·Biochemical and Molecular Medicine·S PitkänenB H Robinson
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Apr 17, 2004·Science·Enza Maria ValenteNicholas W Wood
Dec 13, 2005·The Journal of Allergy and Clinical Immunology·Carlo VancheriNunzio Crimi
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicole ExnerChristian Haass
Feb 16, 2008·Free Radical Biology & Medicine·Bin LiuDaret K St Clair
Aug 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chun ZhouSerge Przedborski
Aug 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Clement A GautierJie Shen
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Fiona Murray-ZmijewskiXin Lu
Mar 13, 2009·The Journal of Biological Chemistry·Ruben K DagdaCharleen T Chu
May 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ling-Yang HaoNancy M Bonini

❮ Previous
Next ❯

Citations

Jan 4, 2012·Journal of Molecular Neuroscience : MN·Ruth Mélida Sánchez-MoraGonzalo Arboleda
Feb 22, 2012·Molecular Neurobiology·Georg AuburgerMarina Jendrach
May 29, 2012·Molecular Neurodegeneration·Clement A GautierJie Shen
May 7, 2013·Progress in Neurobiology·Sudhakar Raja Subramaniam, Marie-Francoise Chesselet
Dec 3, 2014·Biochimica Et Biophysica Acta·Ciara H O'Flanagan, Cora O'Neill
Dec 25, 2012·Free Radical Biology & Medicine·Wei-Lin ChienWen-Mei Fu
Jan 6, 2015·Antioxidants & Redox Signaling·Erin K SteerCharleen T Chu
Jun 13, 2012·Free Radical Biology & Medicine·Micha M M WilhelmusJack van Horssen
Aug 17, 2020·Ageing Research Reviews·Hilal Ahmad MirFirdous A Khanday

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.