Intermediates in the aerobic autoxidation of 6-hydroxydopamine: Relative importance under different reaction conditions

Gee, Pauline; Davison, Allan J.

doi:10.1016/0891-5849(89)90054-3

Cited by 76 publications

(36 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, 6-OHDA is rapidly and non-enzymatically oxidized by molecular oxygen to form hydrogen peroxide and the corresponding p-quinone (21,22). Various downstream mechanisms for its toxicity have been proposed, including the production of reactive oxygen species (ROS), the interaction of one or more of its oxidation products with nucleophilic groups of several intraneuronal proteins, or with peptides like glutathione (21,22), and the inhibition of mitochondrial complexes I and IV (20,23). After the injection of 6-OHDA into the SNpc, dopaminergic neurons undergo degeneration within 24 h. In this study, the injection of 6-OHDA alone reduced the number of SNpc TH-immunopositive neurons by about 35% at 12 h and by 60% at 24 h. Although the coadministration of lactacystin or MG-132 with 6-OHDA reduced the number of TH-immunopositive neurons Immunoreactivities for TH and a-synuclein in the substantia nigra.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats

et al. 2005

View full text Add to dashboard Cite

Abstract. Parkinson's disease is characterized by dopaminergic neuronal death and the presence of Lewy bodies in the substantia nigra pars compacta (SNpc). a -Synuclein and ubiquitin are components of Lewy bodies, but the process of Lewy body formation and the relationship between inclusion formation and dopaminergic neuronal death have not been resolved. In this study, unilateral intranigral microinjection of 6-hydroxydopamine caused a significant loss of tyrosine hydroxylase-immunopositive neurons in both the substantia nigra and striatum and apomorphine-induced contralateral rotation. The co-administration of proteasome inhibitors, such as lactacystin or carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132), significantly prevented both dopaminergic neurodegeneration and apomorphine-induced rotational asymmetry. Proteasome inhibitors markedly formed intracellular protein inclusions labeled by thioflavin-S in the SNpc. Inclusion-like immunoreactivities for a -synuclein and ubiquitin were detected after 4 weeks. These results suggest that proteasome plays an important role in both the early phase of dopaminergic neuronal death and inclusion body formation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Although the oxidation of CA and 6-OHDA by molecular oxygen is broadly discussed in the liter ature (Graham et al, 1978;Graham, 1978;Gee and Davison, 1989; Köhle et al, 1995), the path way and kinetics of these processes are known only in little detail. A plausible sequence of pro ducts formed during CA oxidative transformation is given in Scheme I for the example of DA.…”

Section: Introductionmentioning

confidence: 99%

The Oxidation of Catecholamines and 6-Hydroxydopamine by Molecular Oxygen: Effect of Ascorbate

Roginsky

Barsukova

Bruchelt³

et al. 1997

Zeitschrift Für Naturforschung C

View full text Add to dashboard Cite

Comparative kinetic studies on the oxidation of catecholamines (CA) (dopamine (DA), epi nephrine (EP). norepinephrine (NEP)) serving as a neurom ediator in the sympathetic nervous system, 3,4-dihydroxyphenylalanine (DOPA) and 6-hydroxydopamine (6-OHDA), a wellknown neurotoxic agent, were perform ed in the presence of ascorbate (A scH -) in 50 mM phos phate buffer, pH 7.40, at 37 °C by using a Clark electrode, EPR and the absorption spectros copy. The oxidation of CA and DOPA alone was found to be a self-accelerating process, with quinone products (Q) acting as autocatalysts. The rate of oxygen consumption (Rox) increased with time and reached a steady-state level. A starting value of Ro x increased in the order: EP < DOPA « NEP « DA « 6-OHDA, whereas a steady-state value of Ro x changed in the or der: DOPA < DA < NEP « EP « 6-OHDA. The changes in R0x with time were found to correlate with the resistance of primary Q to the intramolecular cyclization.The effect of A scH -on CA oxidation depended dramatically on whether A scH -was added to non-oxidized or preoxidized CA. Added to non-oxidized CA and DOPA, A scHinhibited their oxidation (but not that of 6-OHDA). For the case of DA, a pronounced lag period was observed by both a Clark electrode and spectrophotometrically. The addition of A scH -to preoxidized CA. DOPA and 6-OHDA induced an increase in R0 x a°d a steadystate concentration of the ascorbyl radical. The kinetic behaviour of the systems was deter mined by two major factors: 1) A scH -suppressed the formation of Q, a catalyst for CA oxidation, most likely due to the reaction of A scH -with the semiquinone formed from CA; 2) Q derived both from CA and 6-OH D A catalyzed A scH -oxidation. The elevated cytotox icity of 6-OHDA was found to be in part caused by the condition that 6-OHDA oxidation was not inhibited by A scH -and by the high efficiency of 6-OHDA as a redox cycling agent in combination with A scH ". These observations explain the very pronounced and prolonged cytotoxicity of 6-OHDA even at low concentrations that increases at elevated concentrations of A scH -.

show abstract

“…6) The toxicological properties of 6-OHDA are related to ROS production, the interaction of one or more of its oxidation products with nucleophilic groups of several intraneuronal proteins, or with peptides like glutathione, 14) and the inhibition of mitochondrial complexes I and IV. 15,16) In this study, DMPO protected nigral DA neurons against 6-OH-DA-induced neurodegeneration in vivo.…”

Section: Resultsmentioning

confidence: 99%

Detoxification of 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration by 5,5-Dimethyl-1-pyrroline <i>N</i>-Oxide, a Radical Trapper, in Hemiparkinsonian Rats

Inden

Kitamura

Takata

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Several useful spin trap agents have been identified for the identification and quantification of biological oxygen radicals. Among them, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been used most frequently as a spin trap agent. The function of DMPO in vivo, however, is still unclear. Thus, the purpose of this study was to evaluate the effect of DMPO in an in vivo model of Parkinson's disease (PD). Rats were microinjected with 6-hydroxydopamine (6-OHDA, 32 nmol) in the presence or absence of DMPO (0.4, 4 nmol). We investigated behavioral and histochemical parameters in this rat model of PD. In addition, to examine the effect of DMPO against oxidative stress, we performed an electron spin resonance (ESR) analysis. Intranigral injection of 6-OHDA alone caused behavioral dysfunction and a massive loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNpc). Co-microinjection of 4 nmol DMPO, but not 0.4 nmol, significantly prevented 6-OHDA-induced behavioral impairments and dopaminergic neurodegeneration. In ESR analysis, DMPO directly trapped hydroxyl radical ( · OH) generated from 6-OHDA and Fe 2 in a concentration-dependent manner. These results suggest that DMPO attenuates 6-OHDA-induced dopaminergic neurodegeneration in a rat model of PD via scavenging · OH, and is a useful tool for biological research of oxidative stresses.

show abstract

Intermediates in the aerobic autoxidation of 6-hydroxydopamine: Relative importance under different reaction conditions

Cited by 76 publications

References 31 publications

Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats

Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats

The Oxidation of Catecholamines and 6-Hydroxydopamine by Molecular Oxygen: Effect of Ascorbate

Detoxification of 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration by 5,5-Dimethyl-1-pyrroline <i>N</i>-Oxide, a Radical Trapper, in Hemiparkinsonian Rats

Contact Info

Product

Resources

About