Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP

Wei, Q.; Yeung, M.; Jurma, O.P.; Andersen, Julie K.

doi:10.1002/(sici)1097-4547(19961215)46:6<666::aid-jnr3>3.3.co;2-4

Cited by 6 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cell culture studies, the impact of MAO activity on cell death, and its specific relation to dopaminergic toxicity, appears largely dependent on the toxin and model under investigation. For example, MAO overexpression has been shown to potentiate the toxicity of dopaminergic neurotoxins MPTP (Wei et al . 1996) and methamphetamine (Wei et al .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protection of intracellular dopamine cytotoxicity by dopamine disposition and metabolism factors

Weingarten

Zhou

2001

Journal of Neurochemistry

View full text Add to dashboard Cite

Dopamine has been hypothesized as a contributing factor for the selective degeneration of dopaminergic neurons in Parkinson's disease. However, the cytotoxic mechanisms of dopamine and its metabolites remain poorly understood. Using a stable aromatic amino acid decarboxylase (AADC) expressing a ®broblast cell line, we previously demonstrated a novel, non-oxidative cytotoxicity of intracellular dopamine. In this study, we further investigate the roles of dopamine metabolism and disposition proteins against intracellular dopamine cytotoxicity by co-expressing these factors in AADC-expressing cells. Our results indicate that overexpression of the vesicular monoamine transporter and monoamine oxidase A-induced protection against intracellular dopamine toxicity, and conversely that pharmacological inhibition of these pathways potentiated L-DOPA toxicity in catecholaminergic PC12 cells. Macrophage migration inhibitory factor and glutathione S-transferase (GST), factors that have recently been shown to be involved in dopamine metabolism, also exhibited a strong protective role against intracellular dopamine cytotoxicity. Our results support a potential role for non-oxidative cytoplasmic dopamine toxicity, and imply that disruption in dopamine disposition and/or metabolism could underlie the progressive degeneration of dopaminergic neurons in Parkinson's disease.

show abstract

Section: Discussionmentioning

confidence: 99%

“…For example, MAO overexpression has been shown to potentiate the toxicity of dopaminergic neurotoxins MPTP (Wei et al . 1996) and methamphetamine (Wei et al . 1997) in PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

Protection of intracellular dopamine cytotoxicity by dopamine disposition and metabolism factors

Weingarten

Zhou

2001

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Reduced glutathione, an important endogenous tripeptide which removes hydrogen peroxide, is significantly reduced in the substantia nigra of postmortem brains of patients with Parkinson's disease (76). The MPTP-induced form of Parkinson's disease is also associated with increased oxidative stress (77). Importantly, therapy with L-dopa may lead to the generation of oxy-radicals (78)' and it is unclear whether such therapy contributes to neuronal damage and accelerates disease progression.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Oxidative injury in the nervous system

Delanty

Dichter

1998

Acta Neurologica Scandinavica

View full text Add to dashboard Cite

A free radical is a highly reactive chemical species that can react with organic macromolecules leading to cell and tissue damage and consequent functional disruption. Free radical or oxidative injury is increasingly recognized as an important factor in the pathophysiology of many human diseases, including those that affect the nervous system. This review summarizes important evidence implicating oxidative injury in the pathogenesis and progression of many important neurological disorders, including cerebrovascular disease, epilepsy, amyotrophic lateral sclerosis, and Huntington's disease. Results of controlled clinical trials of various antioxidant therapies in neurological disease performed to date are also highlighted.

show abstract

“…Two main hypotheses concerning the cause of this neurological damage are currently debated : increased oxidative stress and altered mitochondrial activity. Excessive MAOB expression results in higher levels of free radical production and free radical damage than in control cells (Wei et al, 1996). The oxidation of dopamine is brought about by the action of monoamine oxidase (MAO), as the desamination of dopamine produces not only 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), but also hydrogen peroxide (H 2 O 2 ).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone

Antkiewicz-Michaluk

Wardas

Michaluk

et al. 2004

Int. J. Neuropsychopharm.

View full text Add to dashboard Cite

The aim of this paper was to investigate whether rotenone, a pesticide causing experimental parkinsonism, causes direct damage to dopaminergic structure when injected intracerebrally and whether this action may be prevented by peripheral administration of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous compound with anti-dopaminergic activity. Male Wistar rats were injected unilaterally into the median forebrain bundle with 2 microg rotenone, and received 1MeTIQ, 50 mg/kg i.p. 1 h before and then daily for 21 d. To compare the effect of intracerebral and peripheral treatment, rotenone was also given once or for 7 d in a dose of 10 mg/kg s.c. Dopamine, serotonin and their metabolites were assessed by HPLC in the substantia nigra and striatum. While a single subcutaneous rotenone dose did not produce any change in striatal dopamine metabolism, the multiple treatments resulted in changes suggesting a shift in the metabolism towards oxidative desamination and reduction of O-methylation. In contrast to systemic injections, intracerebral-administered rotenone produced a decrease in dopamine and its metabolites content in the striatum (dopamine decrease by 70%) and substantia nigra (dopamine decrease by 35%), without affecting the serotonin system. As those changes were observed 21 d after the injection of rotenone, they suggest a durable neurotoxic effect. The treatment with 1MeTIQ strongly reduced the fall of striatal dopamine concentration. The data suggest that rotenone given peripherally affects metabolic processes in dopaminergic neurons, and this seems to result from its neurotoxic action, which may be observed after an intracerebral injection. 1MeTIQ is able to counteract the damaging action of rotenone and seems to be a potential neuroprotective agent.

show abstract

Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP

Cited by 6 publications

References 13 publications

Protection of intracellular dopamine cytotoxicity by dopamine disposition and metabolism factors

Protection of intracellular dopamine cytotoxicity by dopamine disposition and metabolism factors

Oxidative injury in the nervous system

Protective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline against dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone

Contact Info

Product

Resources

About