HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 26, 24078-24089, June 27, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/26/24078    most recent M302051200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, H. Articles by Kalyanaraman, B. Search for Related Content PubMed PubMed Citation Articles by Zhang, H. Articles by Kalyanaraman, B. Social Bookmarking                      What's this?

Bicarbonate-dependent Peroxidase Activity of Human Cu,Zn-Superoxide Dismutase Induces Covalent Aggregation of Protein

INTERMEDIACY OF TRYPTOPHAN-DERIVED OXIDATION PRODUCTS^*

Hao Zhang , Christopher Andrekopoulos , Joy Joseph , Karunakaran Chandran , Hakim Karoui , John P. Crow ¶ and B. Kalyanaraman  ||

From the Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, Laboratoire Structure et Réactivité des Espèces Paramagnétiques, Université de Provence, Marseille, France, and the ^¶Departments of Anesthesiology and Pharmacology/Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35233

This study addresses the mechanism of covalent aggregation of human Cu,Zn-superoxide dismutase (hSOD1^WT) induced by bicarbonate ()-mediated peroxidase activity. Higher molecular weight species (apparent dimers and trimers) of hSOD1^WT were formed from incubation mixtures containing hSOD1^WT, H₂O₂, and . -dependent peroxidase activity and covalent aggregation of hSOD1^WT were mimicked by UV photolysis of hSOD1-WT in the presence of a [Co(NH₃)₅CO₃]⁺ complex that generates the carbonate radical anion (). Human SOD1^WT has but one aromatic residue, a tryptophan residue (Trp-32) on the surface of the protein. Substitution of Trp-32 with phenylalanine produced a mutant (hSOD1^W32F) that exhibits -dependent peroxidase activity similar to wild-type enzyme. However, unlike hSOD1^WT, incubations containing hSOD1^W32F,H₂O₂, and did not result in covalent aggregation of SOD1. These findings indicate that Trp-32 is crucial for -induced covalent aggregation of hSOD1^WT. Spin-trapping results revealed the formation of the Trp-32 radical from hSOD1^WT, but not from hSOD1^W32F. Spin traps also inhibited the covalent aggregation of hSOD1^WT. Fluorescence experiments revealed that Trp-32 was further oxidized by , forming kynurenine-type products in the presence of oxygen. Molecular oxygen was needed for /H₂O₂-dependent aggregation of hSOD1^WT, implicating a role for a Trp-32-dependent peroxidative reaction in the covalent aggregation of hSOD1^WT. Taken together, these results indicate that Trp-32 oxidation is crucial for covalent aggregation of hSOD1. Implications of -dependent SOD1 peroxidase activity in amyotrophic lateral sclerosis disease are discussed.

Received for publication, February 26, 2003 , and in revised form, April 5, 2003.

^* This work was supported by National Institutes of Health Grants RR01008, NS40494, and NS40819 (to J. P. C.) and the ALS Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Biophysics Research Institute, Medical College of Wisconsin, 8701 Watertown Plank Rd., P.O. Box 26509, Milwaukee, WI 53226-0509. Tel.: 414-456-4035; Fax: 414-456-6512; E-mail: balarama{at}mcw.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. A. Vargas, S. Djonovic, S. A. Sukno, and C. M. Kenerley Dimerization Controls the Activity of Fungal Elicitors That Trigger Systemic Resistance in Plants J. Biol. Chem., July 11, 2008; 283(28): 19804 - 19815. [Abstract] [Full Text] [PDF]

				N. Fujiwara, M. Nakano, S. Kato, D. Yoshihara, T. Ookawara, H. Eguchi, N. Taniguchi, and K. Suzuki Oxidative Modification to Cysteine Sulfonic Acid of Cys111 in Human Copper-Zinc Superoxide Dismutase J. Biol. Chem., December 7, 2007; 282(49): 35933 - 35944. [Abstract] [Full Text] [PDF]

				D. M. Taylor, B. F. Gibbs, E. Kabashi, S. Minotti, H. D. Durham, and J. N. Agar Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis J. Biol. Chem., June 1, 2007; 282(22): 16329 - 16335. [Abstract] [Full Text] [PDF]

				Y. Furukawa, R. Fu, H.-X. Deng, T. Siddique, and T. V. O'Halloran From the Cover: Disulfide cross-linked protein represents a significant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice PNAS, May 2, 2006; 103(18): 7148 - 7153. [Abstract] [Full Text] [PDF]

				F. Yamakura, T. Matsumoto, K. Ikeda, H. Taka, T. Fujimura, K. Murayama, E. Watanabe, M. Tamaki, T. Imai, and K. Takamori Nitrated and Oxidized Products of a Single Tryptophan Residue in Human Cu,Zn-Superoxide Dismutase Treated with Either Peroxynitrite-Carbon Dioxide or Myeloperoxidase-Hydrogen Peroxide-Nitrite J. Biochem., July 1, 2005; 138(1): 57 - 69. [Abstract] [Full Text] [PDF]

				Y. Furukawa and T. V. O'Halloran Amyotrophic Lateral Sclerosis Mutations Have the Greatest Destabilizing Effect on the Apo- and Reduced Form of SOD1, Leading to Unfolding and Oxidative Aggregation J. Biol. Chem., April 29, 2005; 280(17): 17266 - 17274. [Abstract] [Full Text] [PDF]

				M. G. Bonini, S. Miyamoto, P. D. Mascio, and O. Augusto Production of the Carbonate Radical Anion during Xanthine Oxidase Turnover in the Presence of Bicarbonate J. Biol. Chem., December 10, 2004; 279(50): 51836 - 51843. [Abstract] [Full Text] [PDF]

				S. I. Liochev and I. Fridovich Carbon dioxide mediates Mn(II)-catalyzed decomposition of hydrogen peroxide and peroxidation reactions PNAS, August 24, 2004; 101(34): 12485 - 12490. [Abstract] [Full Text] [PDF]

				C. Karunakaran, H. Zhang, J. P. Crow, W. E. Antholine, and B. Kalyanaraman Direct Probing of Copper Active Site and Free Radical Formed during Bicarbonate-dependent Peroxidase Activity of Bovine and Human Copper,Zinc-superoxide Dismutases: LOW-TEMPERATURE ELECTRON PARAMAGNETIC RESONANCE AND ELECTRON NUCLEAR DOUBLE RESONANCE STUDIES J. Biol. Chem., July 30, 2004; 279(31): 32534 - 32540. [Abstract] [Full Text] [PDF]

				X. Fu, J. L. F. Kao, C. Bergt, S. Y. Kassim, N. P. Huq, A. d'Avignon, W. C. Parks, R. P. Mecham, and J. W. Heinecke Oxidative Cross-linking of Tryptophan to Glycine Restrains Matrix Metalloproteinase Activity: SPECIFIC STRUCTURAL MOTIFS CONTROL PROTEIN OXIDATION J. Biol. Chem., February 20, 2004; 279(8): 6209 - 6212. [Abstract] [Full Text] [PDF]