|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 33, 30964-30970, August 17, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
Formation of Highly Reactive
-Ketoaldehydes (Neuroketals) as
Products of the Neuroprostane Pathway*
-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.
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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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 |