title: Cysteine oxidation of tau and microtubule-associated protein-2 by peroxynitrite: modulation of microtubule assembly kinetics by the thioredoxin reductase system.
abstract: Alterations in the redox status of proteins have been implicated in the pathology of several neurodegenerative conditions including Alzheimer and Parkinson diseases. We report that peroxynitrite- and hydrogen peroxide-induced disulfides in the neuron-specific microtubule-associated proteins tau and microtubule-associated protein-2 are substrates for the ubiquitous thioredoxin reductase system composed of thioredoxin reductase, human or Escherichia coli thioredoxin, and NADPH. Tau and microtubule-associated protein-2 cysteine oxidation and reduction were quantitated by monitoring the incorporation of 5-iodoacetamidofluorescein, a thiol-specific labeling reagent. Cysteine oxidation of tau and microtubule-associated protein-2 to disulfides altered the ability of the proteins to promote the assembly of microtubules from purified porcine tubulin. Treatment of tau and microtubule-associated protein-2 with either the thioredoxin reductase system or small molecule reductants fully restores the ability of the MAPs to promote microtubule assembly. Thus changes in the redox state of microtubule-associated proteins may regulate microtubule polymerization in vivo.
authors.affiliation: Department of Chemistry, The College of William and Mary, Williamsburg, VA 23187-8795, USA. lmland@wm.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Landino
authors.forename: Tabor E
authors.initials: TE
authors.lastname: Skreslet
authors.forename: Jane A
authors.initials: JA
authors.lastname: Alston
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005452:Fluoresceins / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism* / Q000494:pharmacology; D013552:Swine; D013696:Temperature; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004220:Disulfides; D005452:Fluoresceins; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D030421:Peroxynitrous Acid; D013879:Thioredoxins; C015296:5-iodoacetamidofluorescein; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine; D010100:Oxygen