Clinical and biochemical consequences of copper-histidine therapy in Menkes disease

Kreuder, Joachim; Otten, A; Fuder, H.; Tümer, Zeynep; Tønnesen, T.; Horn, Nina; Dralle, D.

doi:10.1007/bf02073380

Cited by 68 publications

(40 citation statements)

References 33 publications

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“…In light of our findings, it is notable that bacterial infections, especially those of the respiratory tract, are commonly reported in infants with Menkes disease, in whom genetic mutations in the ATP7A gene give rise to copper deficiency (43)(44)(45)(46). However, it is uncertain whether this susceptibility to infections arises from defects in ATP7A-dependent activities of macrophages or impairment of other copper-requiring processes.…”

Section: Discussionmentioning

confidence: 70%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

449

547

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Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-␥ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, suggesting a role for ATP7A-dependent copper transport in the bactericidal activity of macrophages. Significantly, a copper-sensitive mutant of Escherichia coli lacking the CopA copper-transporting ATPase was hypersensitive to killing by RAW264.7 macrophages, and this phenotype was dependent on ATP7A expression. Collectively, these data suggest that copper-transporting ATPases, CopA and ATP7A, in both bacteria and macrophage are unique determinants of bacteria survival and identify an unexpected role for copper at the hostpathogen interface.

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Section: Discussionmentioning

confidence: 70%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

449

547

View full text Add to dashboard Cite

show abstract

“…Whether CTR1 and ATP7A play critical roles in killing other bacterial pathogens such as M. tuberculosis and S. typhimurium in vitro and in vivo is the subject of ongoing investigations. However, consistent with a role for ATP7A in immune defense, it is notable that patients with Menkes disease who lack a functional ATP7A copper transporter have increased susceptibility to infection of the bladder and lungs (81)(82)(83)(84).…”

Section: Importance Of Mammalian Copper Transporters In Macrophage Bamentioning

confidence: 83%

Copper Homeostasis at the Host-Pathogen Interface

Hodgkinson

Petris

2012

Journal of Biological Chemistry

269

243

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The trace element copper is indispensable for all aerobic life forms. Its ability to cycle between two oxidation states, Cu 1؉ and Cu 2؉ , has been harnessed by a wide array of metalloenzymes that catalyze electron transfer reactions. The metabolic needs for copper are sustained by a complex series of transporters and carrier proteins that regulate its intracellular accumulation and distribution in both pathogenic microbes and their animal hosts. However, copper is also potentially toxic due in part to its ability to generate reactive oxygen species. Recent studies suggest that the macrophage phagosome accumulates copper during bacterial infection, which may constitute an important mechanism of killing. Bacterial countermeasures include the up-regulation of copper export and detoxification genes during infection, which studies suggest are important determinants of virulence. In this minireview, we summarize recent developments that suggest an emerging role for copper as an unexpected component in determining the outcome of host-pathogen interactions.

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“…Among the available copper compounds, copper histidine has proved to be the most effective. [57][58] Positive outcome of copper-histidine supplementation is dependent on early initiation and presence of at least partially functional ATP7A.…”

Section: Carrier Identification and Prenatal Diagnosismentioning

confidence: 99%