Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells

• Published in: Journal of neuroscience research 2003-03, Vol.71 (6), p.863-870
• Main Authors: Gómez-Ramos, Alberto, Díaz-Nido, Javier, Smith, Mark A., Perry, George, Avila, Jesús
• Format: Article
• Language: English
• Subjects: acrolein; Acrolein - toxicity; Animals; Arachidonic Acid - pharmacology; Blotting, Western; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Enzyme Inhibitors - pharmacology; GSK3; Humans; Imidazoles - pharmacology; Lipid Peroxidation - physiology; Lithium - pharmacology; Mice; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Neuroblastoma - metabolism; Neurons - drug effects; Neurons - metabolism; p38; p38 Mitogen-Activated Protein Kinases; Phosphorylation - drug effects; phosphorylation sites; Pyridines - pharmacology; tau; tau Proteins - drug effects; tau Proteins - metabolism; Tumor Cells, Cultured
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10525

A hallmark of several neurodegenerative disorders, including Alzheimer's disease and tauopathies, is the hyperphosphorylation of the microtubule‐associated protein tau. Tau phosphorylation by proline‐directed and non‐proline‐directed protein kinases has been tested using antibodies PHF1 and 12E8, respectively. The effect of the lipid peroxidation product acrolein on these modes of phosphorylation has been assayed. We have found that acrolein, a peroxidation product from arachidonic acid, increases the phosphorylation of tau at the site recognized by PHF‐1 both in human neuroblastoma cells and in primary cultures of mouse embryo cortical neurons. Whereas the basal phosphorylation of tau protein at the PHF1 site seems to be largely mediated by glycogen synthase kinase‐3 (which is also activated in response to Aβ peptide), the acrolein‐induced tau hyperphosphorylation at the same site is also due to p38 stress‐activated kinase. These results support the view that oxidative stress and subsequent formation of lipid peroxidation products may contribute to tau protein phosphorylation in Alzheimer's disease and tauopathies. © 2002 Wiley‐Liss, Inc.