Stabilization and Reduced Cytotoxicity of Amyloid Beta Aggregates in the Presence of Catechol Neurotransmitters.

Oligomeric aggregates of the amyloid-beta (Aβ) peptide have been implicated as the toxic species for Alzheimer's disease by contributing to oxidative cytotoxicity and physical disruption in cell membranes in the brain. Recent evidence points to the ability of the catecholamine neurotransmitter dopamine in the presence of copper ions to both stabilize oligomers and decrease the toxic effects of these oligomers. Based on these results, physical characterization of aggregates and subsequent cell studies with a neuroblastoma line were performed that show both dopamine and the related neurotransmitter, norepinephrine, can stabilize oligomers and decrease toxicity of Aβ aggregates without copper present.

Stabilization of Alpha-Synuclein Oligomers In Vitro by the Neurotransmitters, Dopamine and Norepinephrine: The Effect of Oxidized Catecholamines.

Aggregation of the protein alpha-synuclein has been identified in the pathogenesis of Parkinson's disease and is initiated by the folding of the protein monomer into an amyloid form of insoluble fibrils. The neurotransmitters dopamine and norepinephrine have been shown to both inhibit the formation of these fibrils and disaggregate existing fibrils, yielding the more toxic oligomeric form of α-synuclein. This study characterizes the stable oligomers formed through the aggregation and disaggregation processes in the presence of these catecholamines, and suggests differences in oligomer formation depending on the extent of oxidation of the neurotransmitter at the time of oligomerization.

Effect of unsaturation in fatty acids on the binding and oxidation by myeloperoxidase: ramifications for the initiation of atherosclerosis.

Oxidation of low density lipoproteins (LDL) in the presence of myeloperoxidase and subsequent uptake of the oxidized LDL by specialized receptors on macrophages has been suggested as an initiating event of atherosclerosis. Oxidized fatty acid chains within the glycerophospholipids of LDL have been implicated as the recognition feature by the receptors. The ability of three fatty acids (oleic, linoleic, and arachidonic acids) typically contained in the lipid portion of the glycerophospholipids to bind and be oxidized by myeloperoxidase was measured by spectroscopically observing interactions of the lipids with the heme prosthetic group of the enzyme.

O(2)- and H(2)O(2)-dependent verdoheme degradation by heme oxygenase: reaction mechanisms and potential physiological roles of the dual pathway degradation.

Heme oxygenase (HO) catalyzes the catabolism of heme to biliverdin, CO, and a free iron through three successive oxygenation steps. The third oxygenation, oxidative degradation of verdoheme to biliverdin, has been the least understood step despite its importance in regulating HO activity. We have examined in detail the degradation of a synthetic verdoheme IXalpha complexed with rat HO-1.

Stereoselectivity of each of the three steps of the heme oxygenase reaction: hemin to meso-hydroxyhemin, meso-hydroxyhemin to verdoheme, and verdoheme to biliverdin.

Heme oxygenase catalyzes the regiospecific oxidation of hemin to biliverdin IXalpha with concomitant liberation of CO and iron by three sequential monooxygenase reactions. The alpha-regioselectivity of heme oxygenase has been thought to result from the regioselective oxygenation of the heme alpha-meso position at the first step, which leads to the reaction pathway via meso-hydroxyheme IXalpha and verdoheme IXalpha intermediates. However, recent reports concerning heme oxygenase forming biliverdin isomers other than biliverdin IXalpha raise a question whether heme oxygenase can degrade meso-hydroxyhemin and isomers other than the alpha-isomers.