Portal de Periódicos da CAPES

The Nitration Product 5-Nitro-γ-tocopherol Is Increased in the Alzheimer Brain

2002; Elsevier BV; Volume: 6; Issue: 2 Linguagem: Inglês

10.1006/niox.2001.0399

1089-8611

Kelly S. Williamson, S. Prasad Gabbita, Shenyun Mou, Melinda West, Quentin N. Pye, William R. Markesbery, Robert V. Cooney, Paula Grammas, Ulrich Reimann‐Philipp, Robert A. Floyd, Kenneth Hensley,

Mitochondrial Function and Pathology

Oxidative stress and quasi-inflammatory processes recently have been recognized as contributing factors in the pathogenesis of Alzheimer's disease (AD). Reactive nitrating species have specifically been implicated in AD based on immunochemical and instrumental detection of nitrotyrosine in AD brain protein. The significance of lipid-phase nitration has not been investigated in AD. This study documents a significant two- to threefold increase in the lipid nitration product 5-nitro-γ-tocopherol in affected regions of the AD brain as determined by high-performance liquid chromatography with electrochemical detection. In a bioassay to compare the relative potency of α-tocopherol and γ-tocopherol against nitrative stress, rat brain mitochondria were exposed to the peroxynitrite-generating compound SIN-1. The oxidation-sensitive Kreb's cycle enzyme α-ketoglutarate dehydrogenase was inactivated by SIN-1, in a manner that could be significantly attenuated by γ-tocopherol (at <10 μM) but not by α-tocopherol. These data indicate that nitric oxide-derived species are significant contributors to lipid oxidation in the AD brain. The findings are discussed in reference to the neuroinflammatory hypothesis of AD and the possible role of γ-tocopherol as a major lipid-phase scavenger of reactive nitrogen species.