67992-45-4Relevant academic research and scientific papers
Regulatory Activities of Dopamine and Its Derivatives towards Metal-Free and Metal-Induced Amyloid-β Aggregation, Oxidative Stress, and Inflammation in Alzheimer's Disease
Nam, Eunju,Derrick, Jeffrey S.,Lee, Seunghee,Kang, Juhye,Han, Jiyeon,Lee, Shin Jung C.,Chung, Su Wol,Lim, Mi Hee
, (2018/05/31)
A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked to the pathology of dementia; however, the involvement of DA and its structural analogues in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that DA and its rationally designed structural derivatives (1-6) based on DA's oxidative transformation are able to modulate multiple pathological elements found in AD [i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ (metal-Aβ), and reactive oxygen species (ROS)], with demonstration of detailed molecular-level mechanisms. Our multidisciplinary studies validate that the protective effects of DA and its derivatives on Aβ aggregation and Aβ-mediated toxicity are induced by their oxidative transformation with concomitant ROS generation under aerobic conditions. In particular, DA and the derivatives (i.e., 3 and 4) show their noticeable anti-amyloidogenic ability towards metal-free Aβ and/or metal-Aβ, verified to occur via their oxidative transformation that facilitates Aβ oxidation. Moreover, in primary pan-microglial marker (CD11b)-positive cells, the major producers of inflammatory mediators in the brain, DA and its derivatives significantly diminish inflammation and oxidative stress triggered by lipopolysaccharides and Aβ through the reduced induction of inflammatory mediators as well as upregulated expression of heme oxygenase-1, the enzyme responsible for production of antioxidants. Collectively, we illuminate how DA and its derivatives can prevent multiple pathological features found in AD with identification of molecular-level mechanisms. The overall studies could advance our understanding regarding distinct roles of neurotransmitters in AD and identify key interactions for alleviation of AD pathology.
Inhibition of the Fe(III)-catalyzed dopamine oxidation by ATP and its relevance to oxidative stress in Parkinson's disease
Jiang, Dianlu,Shi, Shuyun,Zhang, Lin,Liu, Lin,Ding, Bingrong,Zhao, Bingqing,Yagnik, Gargey,Zhou, Feimeng
, p. 1305 - 1313 (2013/10/01)
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic cells, which implicates a role of dopamine (DA) in the etiology of PD. A possible DA degradation pathway is the Fe(III)-catalyzed oxidation of DA by oxygen, which produces neuronal toxins as side products. We investigated how ATP, an abundant and ubiquitous molecule in cellular milieu, affects the catalytic oxidation reaction of dopamine. For the first time, a unique, highly stable DA-Fe(III)-ATP ternary complex was formed and characterized in vitro. ATP as a ligand shifts the catecholate-Fe(III) ligand metal charge transfer (LMCT) band to a longer wavelength and the redox potentials of both DA and the Fe(III) center in the ternary complex. Remarkably, the additional ligation by ATP was found to significantly reverse the catalytic effect of the Fe(III) center on the DA oxidation. The reversal is attributed to the full occupation of the Fe(III) coordination sites by ATP and DA, which blocks O2 from accessing the Fe(III) center and its further reaction with DA. The biological relevance of this complex is strongly implicated by the identification of the ternary complex in the substantia nigra of rat brain and its attenuation of cytotoxicity of the Fe(III)-DA complex. Since ATP deficiency accompanies PD and neurotoxin 1-methyl-4-phenylpyridinium (MPP+) induced PD, deficiency of ATP and the resultant impairment toward the inhibition of the Fe(III)-catalyzed DA oxidation may contribute to the pathogenesis of PD. Our finding provides new insight into the pathways of DA oxidation and its relationship with synaptic activity.
The participation of Singlet Oxygen in Dye-Sensitized Photooxidation Reaction of Catecholamines
Kruk, I.
, p. 607 - 613 (2007/10/02)
The photooxidation of catecholamines (adrenaline, noradrenaline and dopamine) sensitized by methylene blue (MB), rose bengal (RB) and fluoresceine (FL) proceed via aminochromes and an indolic pathway.In D2O rate constants of sensitized photooxidation are increased for about 2,7 times over rates in water. 1,3-diphenylisobenzofuran (DPBF), 1,4-diazobicyclooctane (DABCO) and azide anion were more effective inhibitors of the reaction in D2O than in H2O.Superoxide dismutase markedly decreases the rates of photooxidation in H2O and in D2O.Isotope effects and 1O2-quenchers sensitivities indicate that singlet oxygen participates on photooxidation processes of catecholamines.
