Prostaglandin H Synthetase‐Mediated Metabolism of Dopamine: Implication for Parkinson's Disease

Mattammal, Michael B.; Strong, Randy; Lakshmi, Vijaya M.; Chung, Hyung D.; Stephenson, Alan H.

doi:10.1046/j.1471-4159.1995.64041645.x

Cited by 145 publications

(84 citation statements)

References 30 publications

(44 reference statements)

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“…Consistent with the previous report [40] , here we also find that chronic stress could cause anxiety-like behavior and cognitive dysfunctions. When exposed to the mirror chamber, the chronic stressed animals exhibited anxiety, as revealed by decreases in the number of entries in mirror chamber and time spent in mirror chamber.…”

Section: Discussionsupporting

confidence: 93%

Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress

2010

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Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also play a key role in the pathophysiology of various brain-related disorders. The present study was aimed to explore the protective effect of cyclooxygenase inhibitors on stress by using an animal model of chronic stress. Methods The animals were forced to swim individually for a period of 6 min every day for 15 d. Then, the behavior (locomotor activity, anxiety and memory) and biochemical (lipid peroxidation, nitrite level, reduced glutathione, and catalase) alterations were assessed. Results Forced swimming for 15 d caused impaired locomotor activity, anxiety-like behavior and decreased percentage of memory retention, as compared to naïve mice (without chronic fatigue treatment). Biochemical analysis revealed significant increases in lipid peroxidation and nitrite level, while levels of reduced glutathione and catalase activity were both decreased. Chronic treatment with naproxen (14 mg/kg, i.p.), rofecoxib (5 mg/kg, i.p.), meloxicam (5 mg/kg, i.p.), nimesulide (5 mg/kg, i.p.) and valdecoxib (10 mg/kg, i.p.) significantly attenuated these behavioral and biochemical (oxidative damage) alterations in chronic-stressed mice. ConclusionThe cyclooxygenase inhibitors could be used in the management of chronic fatigue-like conditions.

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Section: Discussionsupporting

confidence: 93%

Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress

2010

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“…In the presence of reducing co-substrates, Intermediates I and II are returned to resting state (36). Phenolic compounds such as phenol (15), luminol (37), and dopamine (38,39) are preferred as reducing co-substrates. We hypothesized that the sole tyrosine residue of human A␤ could be a target for the peroxidative activity of COX-2 and that tyrosyl radicals of human A␤ formed by the reduction of oxidized COX-2 will cross-link each other to generate DT (40), emulating the reaction of HRP with A␤ (13).…”

Section: Cox-2 Cross-links A␤mentioning

confidence: 99%

Peroxidase Activity of Cyclooxygenase-2 (COX-2) Cross-links β-Amyloid (Aβ) and Generates Aβ-COX-2 Hetero-oligomers That Are Increased in Alzheimer's Disease

Nagano

Huang

Moir

et al. 2004

Journal of Biological Chemistry

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Oxidative stress is associated with the neuropathology of Alzheimer's disease. We have previously shown that human A␤ has the ability to reduce Fe(III) and Cu(II) and produce hydrogen peroxide coupled with these metals, which is correlated with toxicity against primary neuronal cells. Cyclooxygenase (COX)-2 expression is linked to the progression and severity of pathology in AD. COX is a heme-containing enzyme that produces prostaglandins, and the enzyme also possesses peroxidase activity. Here we investigated the possibility of direct interaction between human A␤ and COX-2 being mediated by the peroxidase activity. Human A␤ formed dimers when it was reacted with COX-2 and hydrogen peroxide. Moreover, the peptide formed a cross-linked complex directly with COX-2. Such crosslinking was not observed with rat A␤, and the sole tyrosine residue specific for human A␤ might therefore be the site of cross-linking. Similar complexes of A␤ and COX-2 were detected in post-mortem brain samples in greater amounts in AD tissue than in age-matched controls. COX-2-mediated cross-linking may inhibit A␤ catabolism and possibly generate toxic intracellular forms of oligomeric A␤.

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“…There has been some debate regarding the expression of tyrosinase in the substantia nigra (Xu et al, 1997;Gimenez et al, 2003), but other enzymes such as peroxidases, including prostaglandin H synthase, can also catalyze the oxidation of dopamine to its quinone derivatives (Hastings, 1995;Mattammal et al, 1995). In addition to the generation of reactive quinone metabolites, autoxidation of many of the intermediates in this pathway is also possible with concomitant generation of reactive oxygen species (Graham, 1978;Graham et al, 1978;Segura-Aguilar et al, 1998).…”

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confidence: 99%

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

Zafar¹,

Siegel²,

Ross³

2006

Mol Pharmacol

106

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We examined the ability of oxidation products of dopamine, DOPA, and 3,4-dihydroxyphenylacetic acid (DOPAC) to inhibit proteasomal activity. Dopamine, DOPA, and DOPAC underwent tyrosinase-catalyzed oxidation to generate aminochrome, dopachrome, and furanoquinone, respectively. In these studies, the oxidation of dopamine by tyrosinase generated product(s) that inhibited the proteasome, and proteasomal inhibition correlated with the presence of the UV-visible spectrum of aminochrome. The addition of superoxide dismutase and catalase did not prevent proteasomal inhibition. The addition of NADH and the quinone reductase NAD(P)H:quinone oxidoreductase 1 (NQO1) protected against aminochromeinduced proteasome inhibition. Although NQO1 protected against dopamine-induced proteasomal inhibition, the metabolism of aminochrome by NQO1 led to oxygen uptake because of the generation of a redox-labile cyclized hydroquinone, further demonstrating the lack of involvement of oxygen radicals in proteasomal inhibition. DOPA underwent tyrosinase-catalyzed oxidation to form dopachrome, and similar to aminochrome, proteasomal inhibition correlated with the presence of a dopachrome UV-visible spectrum. The inclusion of NQO1 did not protect against proteasomal inhibition induced by dopachrome. Oxidation of DOPAC by tyrosinase generated furanoquinone, which was a poor proteasome inhibitor. These studies demonstrate that oxidation products, including cyclized quinones derived from dopamine and related compounds, rather than oxygen radicals have the ability to inhibit the proteasome. They also suggest an important protective role for NQO1 in protecting against dopamine-induced proteasomal inhibition. The ability of endogenous intermediates formed during dopaminergic metabolism to cause proteasomal inhibition provides a potential basis for the selectivity of dopaminergic neuron damage in Parkinson's disease.Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by destruction of dopamine containing neurons in the substantia nigra pars compacta coupled with the formation of neuronal cytoplasmic inclusions known as Lewy bodies (Olanow and Tatton, 1999). Several lines of evidence have implicated failure of the ubiquitin proteasomal system (UPS) as central in the pathogenesis of PD, and a number of excellent, recent reviews have summarized the evidence linking defects in the UPS to both familial and sporadic PD

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Prostaglandin H Synthetase‐Mediated Metabolism of Dopamine: Implication for Parkinson's Disease

Cited by 145 publications

References 30 publications

Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress

Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress

Peroxidase Activity of Cyclooxygenase-2 (COX-2) Cross-links β-Amyloid (Aβ) and Generates Aβ-COX-2 Hetero-oligomers That Are Increased in Alzheimer's Disease

A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition

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