Paradoxical effects of copper and manganese on brain mitochondrial function

Heron, Paula; Cousins, Katherine L.; Boyd, C.; Daya, Santy

doi:10.1016/s0024-3205(01)00948-1

Cited by 29 publications

(19 citation statements)

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“…This enzyme is representative of maximal aerobic capacity and has been found to account for 90% of total respiration (Hochachka et al 1970). In the mammalian literature, Cd and Cu have been reported to decrease aerobic capacities by inhibiting mitochondrial enzymes or affecting the integrity of mitochondrial membranes (Sokol et al 1993;Pourahmad and O'Brien 1999;Heron et al 2001). With peak liver Cu concentrations in summer in Whitson fish corresponding with lower muscle CS values, our data suggest that toxic effects may occur at the mitochondrial level in Cu-contaminated fish.…”

Section: Discussionmentioning

confidence: 51%

Seasonal variations in tissue metabolic capacities of yellow perch (Perca flavescens) from clean and metal-contaminated environments

Audet¹,

Couture²

2003

Can. J. Fish. Aquat. Sci.

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This study examined seasonal variations in tissue metal contamination and physiological condition of yellow perch (Perca flavescens) from a clean lake (Halfway Lake) and a metal-contaminated environment (Whitson Lake) in spring, summer, and fall of 1999. Dietary metal content influenced liver metal concentrations, especially for cadmium. Fulton's condition factor (FCF), an indicator of recent feeding activity, was lower in Whitson fish except in summer, when higher FCF values corresponded with higher liver copper concentrations, presumably because of higher feeding rate. Tissue protein concentrations and indicators of biosynthetic capacities (nucleoside diphosphate kinase and RNA/DNA ratios) suggested lower biosynthesis in Whitson fish. Muscle aerobic and anaerobic capacities (using citrate synthase and lactate dehydrogenase as indicators, respectively) were consistently lower in Whitson fish, with maximal differences in summer. In contrast, although liver aerobic capacities were generally comparable among populations, anaerobic capacities were much higher in Whitson fish. Finally, gill sodium/potassium adenosinetriphosphatase (Na + /K + ATPase) activity peaked in the spring in fish from both lakes, and higher activities were correlated with elevated gill copper concentrations. This study highlights the importance of seasonal variations in tissue metal concentrations and fish condition. This information is essential to evaluate the extent of impairment in condition faced by metalcontaminated wild fish.Résumé : Nous avons examiné les variations saisonnières de la contamination des tissus par les métaux et de la condition physiologique de perchaudes (Perca flavescens) d'un milieu propre (lac Halfway) et d'un milieu contaminé par les métaux (lac Whitson) au printemps, à l'été et à l'automne 1999. Le contenu en métaux du régime alimentaire influence la concentration hépatique des métaux, en particulier du cadmium. Le coefficient de condition de Fulton (FCF), un indicateur d'activité alimentaire récente, est plus bas chez les poissons du lac Whitson, sauf en été, lorsque les valeurs plus élevées de FCF correspondent à des concentrations plus élevées de cuivre hépatique, sans doute à cause d'un taux d'alimentation plus grand. Les concentrations tissulaires de protéines et les indicateurs du potentiel de biosynthèse (la nucléoside diphosphate kinase et les rapports ARN/ADN) laissent croire à une réduction de la biosynthèse chez les poissons du lac Whitston. Les capacités musculaires aérobies et anaérobies (mesurées respectivement d'après les concentrations de citrate synthase et de lactate déshydrogénase) sont toujours plus basses chez les poissons du lac Whitson et les écarts sont maximaux en été. En revanche, bien que les capacités hépatiques aérobies soient, en général, semblables chez les deux populations, les capacités anaérobies sont beaucoup plus fortes chez les poissons du lac Whitson. Enfin, l'activité de la sodium/potassium adénosinetriphosphatase (ATPase) dans les branchies est maximale au printemps chez les ...

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Section: Discussionmentioning

confidence: 51%

Seasonal variations in tissue metabolic capacities of yellow perch (Perca flavescens) from clean and metal-contaminated environments

Audet¹,

Couture²

2003

Can. J. Fish. Aquat. Sci.

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“…In the TCA cycle, SDH oxidizes succinate to fumarate—both of which inhibit TET and Jumanji C domain-containing histone demethylases. 123 Copper inhibits SDH, 124 as supported by our findings that the lower levels of hepatic SDH in tx-j mice are restored by choline and copper chelation therapy alone and in combination. 103 …”

Section: Copper Overload Mitochondrial Function and Epigenetic Rmentioning

confidence: 55%

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

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Environmental factors, including diet, exercise, stress, and toxins, profoundly impact disease phenotypes. This review examines how Wilson disease (WD), an autosomal recessive genetic disorder, is influenced by genetic and environmental inputs. WD is caused by mutations in the copper-transporter gene ATP7B, leading to the accumulation of copper in the liver and brain, resulting in hepatic, neurological, and psychiatric symptoms. These symptoms range in severity and can first appear anytime between early childhood and old age. Over 300 disease-causing mutations in ATP7B have been identified, but attempts to link genotype to the phenotypic presentation have yielded little insight, prompting investigators to identify alternative mechanisms, such as epigenetics, to explain the highly varied clinical presentation. Further, WD is accompanied by structural and functional abnormalities in mitochondria, potentially altering the production of metabolites that are required for epigenetic regulation of gene expression. Notably, environmental exposure affects the regulation of gene expression and mitochondrial function. We present the “multi-hit” hypothesis of WD progression, which posits that the initial hit is an environmental factor that affects fetal gene expression and epigenetic mechanisms and subsequent “hits” are environmental exposures that occur in the offspring after birth. These environmental hits and subsequent changes in epigenetic regulation may impact copper accumulation and ultimately WD phenotype. Lifestyle changes, including diet, increased physical activity, stress reduction, and toxin avoidance, might influence the presentation and course of WD, and therefore may serve as potential adjunctive or replacement therapies.

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“…Mitochondrial dysfunction is hypothesized to be involved in Mn-induced neurotoxicity (Heron et al, 2001;Zhang et al, 2008;Zhang et al, 2004). Mitochondrial membrane potential (MMP) drives the synthesis of ATP and plays an important role in cell survival (Muramatsu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line

2015

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Paradoxical effects of copper and manganese on brain mitochondrial function

Cited by 29 publications

References 0 publications

Seasonal variations in tissue metabolic capacities of yellow perch (Perca flavescens) from clean and metal-contaminated environments

Seasonal variations in tissue metabolic capacities of yellow perch (Perca flavescens) from clean and metal-contaminated environments

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line

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