Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Bertinato, Jesse; L’Abbé, Mary R.

doi:10.1016/j.jnutbio.2004.02.004

Cited by 188 publications

(99 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A minor decrease in Cu often leads to reduce resistance to infections, fertility problems, chronic fatigue and weakness. Moreover, Cu deficiency can cause anemia, neutropenia, osteoporosis, loss of pigmentation, neurological symptoms and impaired growth [43].…”

Section: Copper (Cu)mentioning

confidence: 99%

Study of Serum Copper and Iron in Children with Chronic Liver Diseases

Ibrahim¹

2013

Anat Physiol

View full text Add to dashboard Cite

Trace elements have a major role as both oxidants and antioxidants, promoting and protecting from tissue damage respectively. As the liver has a pivotal role in trace elements metabolism and consequenyly their bioavailability, we aimed to measure serum levels of essential trace elements in children with chronic liver diseases (CLDs) regardless the etiology and to study their correlation with liver function tests. Serum zinc (Zn), copper (Cu) and iron (Fe); together with other trace elements parameters; were measured in 50 children with CLDs using spectrophotometry and their levels were compared with those age and sex matched healthy children as controls. Serum Cu, Fe, ferritin and transferrin saturation (TS) were significantly higher in the CLDs group than that in the control group; while serum Zn and total iron binding capacity (TIBC) were significantly lower in the CLDs than that in the control group. Serum Fe, Cu, TS and ferritin were positively correlated with biochemical parameters of liver damage; while serum Zn and TIBC were negatively correlated with biochemical parameters of liver damage. These results encourage inclusion of serum Zn, Cu and Fe as biomarkers for monitoring the severity of liver damage during routine assessment of children with CLDs. We recommended caution to avoid excess Fe and Cu intake in children with CLDs. Moreover, Zn supplementation could be encouraged in children with CLDs regardless its etiology.

show abstract

Section: Copper (Cu)mentioning

confidence: 99%

Study of Serum Copper and Iron in Children with Chronic Liver Diseases

Ibrahim¹

2013

Anat Physiol

View full text Add to dashboard Cite

show abstract

“…Hence, the rapid kinetics of copper uptake and release may suggest the presence of a kinetically labile, intracellular copper pool; however, at present, the subcellular location and nature of this pool and the fundamental question of how copper is stored as part of the copper regulatory machinery are elusive. Cytosolic metallothionein has been suggested as a possible buffer ligand for intracellular copper storage (13,14). Despite its high copper affinity, this protein could provide a sufficiently rapid exchange kinetics by means of an associative mechanism as already demonstrated for intermolecular exchange of zinc (15).…”

mentioning

confidence: 99%

Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy

Yang

McRae

Henary

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

364

286

View full text Add to dashboard Cite

Copper is an essential micronutrient that plays a central role for a broad range of biological processes. Although there is compelling evidence that the intracellular milieu does not contain any free copper ions, the rapid kinetics of copper uptake and release suggests the presence of a labile intracellular copper pool. To elucidate the subcellular localization of this pool, we have synthesized and characterized a membrane-permeable, copper-selective fluorescent sensor (CTAP-1). Upon addition of Cu(I), the sensor exhibits a 4.6-fold emission enhancement and reaches a quantum yield of 14%. The sensor exhibits excellent selectivity toward Cu(I), and its emission response is not compromised by the presence of millimolar concentrations of Ca(II) or Mg(II) ions. Variable temperature dynamic NMR studies revealed a rapid Cu(I) self-exchange equilibrium with a low activation barrier of ⌬G ‡ ‫؍‬ 44 kJ⅐mol ؊1 and k obs ϳ 10 5 s ؊1 at room temperature. Mouse fibroblast cells (3T3) incubated with the sensor produced a copper-dependent perinuclear staining pattern, which colocalizes with the subcellular locations of mitochondria and the Golgi apparatus. To evaluate and confirm the sensor's copper-selectivity, we determined the subcellular topography of copper by synchrotron-based x-ray fluorescence microscopy. Furthermore, microprobe x-ray absorption measurements at various subcellular locations showed a near-edge feature that is characteristic for low-coordinate monovalent copper but does not resemble the published spectra for metallothionein or glutathione. The presented data provide a coherent picture with strong evidence for a kinetically labile copper pool, which is predominantly localized in the mitochondria and the Golgi apparatus.photoinduced electron transfer ͉ metal exchange kinetics ͉ dynamic NMR ͉ microprobe x-ray absorption near-edge spectroscopy

show abstract

“…Copper homeostasis can be regulated at the level of copper uptake, distribution, chelation, and export (Askwith and Kaplan 1998;Culotta et al 1999). The cellular proteins that are involved in copper homeostasis, such as importers, exporters, and scavengers, are regulated by different mechanisms including transcriptional activation or repression, changes in protein stability, and the modulation of protein trafficking (Petris et al 2003;Bertinato and L'Abbe 2004;Lane et al 2004).From insects to mammals, heavy metal detoxification is controlled to a large extent by the zinc finger transcription factor MTF-1 (metal response element-binding transcription factor-1, also referred to as metal-responsive transcription factor, or just metal transcription factor) (Westin and Schaffner 1988;Radtke et al 1993;Langmade et al 2000;Giedroc et al 2001;Lichtlen and Schaffner 2001;Zhang et al 2001). Metal response elements (MREs) of consensus TGCRCNC (where R stands for A or G and N for any of the four bases) are cis-regulatory DNA sequences that specifically bind MTF-1 and are essential and sufficient for transcriptional induction upon heavy metal load (Stuart et al 1985;Westin and Schaffner 1988).…”

mentioning

confidence: 99%

Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes

Selvaraj¹,

Balamurugan²,

et al. 2005

View full text Add to dashboard Cite

From insects to mammals, metallothionein genes are induced in response to heavy metal load by the transcription factor MTF-1, which binds to short DNA sequence motifs, termed metal response elements (MREs). Here we describe a novel and seemingly paradoxical role for MTF-1 in Drosophila in that it also mediates transcriptional activation of Ctr1B, a copper importer, upon copper depletion. Activation depends on the same type of MRE motifs in the upstream region of the Ctr1B gene as are normally required for metal induction. Thus, a single transcription factor, MTF-1, plays a direct role in both copper detoxification and acquisition by inducing the expression of metallothioneins and of a copper importer, respectively.

show abstract

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload

Cited by 188 publications

References 85 publications

Study of Serum Copper and Iron in Children with Chronic Liver Diseases

Study of Serum Copper and Iron in Children with Chronic Liver Diseases

Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy

Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes

Contact Info

Product

Resources

About