JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M103768200 on June 18, 2001

J. Biol. Chem., Vol. 276, Issue 33, 30964-30970, August 17, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/33/30964    most recent
M103768200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bernoud-Hubac, N.
Right arrow Articles by Roberts, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bernoud-Hubac, N.
Right arrow Articles by Roberts, L. J., II
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Formation of Highly Reactive gamma -Ketoaldehydes (Neuroketals) as Products of the Neuroprostane Pathway*

Nathalie Bernoud-Hubac, Sean S. Davies, Olivier Boutaud, Thomas J. Montine, and L. Jackson Roberts IIDagger

From the Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, Tennessee 37232-6602

Neuroprostanes are prostaglandin-like compounds produced by free radical-induced peroxidation of docosahexaenoic acid, which is highly enriched in the brain. We previously described the formation of highly reactive gamma -ketoaldehydes (isoketals) as products of the isoprostane pathway of free radical-induced peroxidation of arachidonic acid. We therefore explored whether isoketal-like compounds (neuroketals) are also formed via the neuroprostane pathway. Utilizing mass spectrometric analyses, neuroketals were found to be formed in abundance in vitro during oxidation of docosahexaenoic acid and were formed in greater abundance than isoketals during co-oxidation of docosahexaenoic and arachidonic acid. Neuroketals were shown to rapidly adduct to lysine, forming lactam and Schiff base adducts. Neuroketal lysyl-lactam protein adducts were detected in nonoxidized rat brain synaptosomes at a level of 0.09 ng/mg of protein, which increased 19-fold following oxidation in vitro. Neuroketal lysyl-lactam protein adducts were also detected in vivo in normal human brain at a level of 9.9 ± 3.7 ng/g of brain tissue. These studies identify a new class of highly reactive molecules that may participate in the formation of protein adducts and protein-protein cross-links in neurodegenerative diseases and contribute to the injurious effects of other oxidative pathologies in the brain.

* This work was supported by National Institutes of Health Grants GM42056, GM15431, CA68485, and DK26657.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602. Tel.: 615-343-1816; Fax: 615-343-9446; E-mail: jack.roberts@mcmail.vanderbilt.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
Y. Kawai, H. Fujii, M. Okada, Y. Tsuchie, K. Uchida, and T. Osawa
Formation of N{epsilon}-(succinyl)lysine in vivo: a novel marker for docosahexaenoic acid-derived protein modification
J. Lipid Res., July 1, 2006; 47(7): 1386 - 1398.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. S. Januszewski, N. L. Alderson, A. J. Jenkins, S. R. Thorpe, and J. W. Baynes
Chemical modification of proteins during peroxidation of phospholipids
J. Lipid Res., July 1, 2005; 46(7): 1440 - 1449.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. J. Montine and J. D. Morrow
Fatty Acid Oxidation in the Pathogenesis of Alzheimer's Disease
Am. J. Pathol., May 1, 2005; 166(5): 1283 - 1289.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
P. MONTUSCHI, P. J. BARNES, and L. J. ROBERTS II
Isoprostanes: markers and mediators of oxidative stress
FASEB J, December 1, 2004; 18(15): 1791 - 1800.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
H. F. Poon, V. Calabrese, G. Scapagnini, and D. A. Butterfield
Free Radicals: Key to Brain Aging and Heme Oxygenase as a Cellular Response to Oxidative Stress
J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2004; 59(5): M478 - M493.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. J. Brame, O. Boutaud, S. S. Davies, T. Yang, J. A. Oates, D. Roden, and L. J. Roberts II
Modification of Proteins by Isoketal-containing Oxidized Phospholipids
J. Biol. Chem., April 2, 2004; 279(14): 13447 - 13451.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Boutaud, J. Li, I. Zagol, E. A. Shipp, S. S. Davies, L. J. Roberts II, and J. A. Oates
Levuglandinyl Adducts of Proteins Are Formed via a Prostaglandin H2 Synthase-dependent Pathway after Platelet Activation
J. Biol. Chem., May 2, 2003; 278(19): 16926 - 16928.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.