Reactive nitrogen species lipid oxidation

The impairment of glucose utilization could result from the modification of the glycolytic enzymes under oxidative stress effects. Oxidative stress is an important factor leading to the pathophysiologcal alterations in conformational diseases. Oxidative stress is manifested in protein oxidation, lipid peroxidation, DNA oxidation, and advanced glycation end-products, as well as reactive oxygen species (ROS), and reactive nitrogen species (RNS) formation. Either the oxidants or the products of oxidative stress could modify the proteins or activate other pathways that may lead to additional impairment of cellular functions and to neuronal loss [57, 58]. 

Many questions still remain, such as whether extracellular Ap modulates intracellular Ap, or the mechanism by which Ap accumulation leads to synaptic dysfunction. Other factors, such as oxidative stress, which is extensive in AD, may aid the early accumulation of Ap (Butterfield et al., 2(X)2b). AP peptides stimulate oxidative stress by direct and indirect mechanisms. AP-induced oxidative stress may result from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could react with a number of cellular macromolecular targets including proteins, lipids, carbohydrates, DNA, and RNA. An early marker for oxidative stress is the formation of protein carbonyls, 4-hydroxy-2-tra 5-nonenal (4-HNE) and 3-nitrotyrosme (3-NT), a marker for the nitration of proteins (Butterfield, 2002). Ap peptide can bind to mitochondrial proteins to generate free radicals, or it can promote oxidative stress via neuroinflanunation. Ap peptides stimulate microglial cells to release a neurotoxin, quinoUnic acid, which may also play a role in neurotoxicity (Guillemin et al., 2003). 

A number of NO-derived reactive species can initiate lipid peroxidation, including nitrogen dioxide and, most notably, ONOO , which displays unique properties as a mediator of lipid oxidation. On a molecular basis, ONOO is a more potent lipid oxidant than hydrogen peroxide and, unlike H2O2, it does not require metal catalysis. The one-electron oxidants such as metals, as well as heme proteins and peroxynitrite, are assumed to play an important role in many diseases associated with oxidative stress. Heme proteins such as horseradish peroxidase (HRP) can produce alkylperoxyl radicals through two sequential... 

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