Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: ( a )The schematic of predicted functions of the ATP-driven Cu transporters in noradrenergic neurons. ATP7A is located in the trans-Golgi network and delivers Cu cofactor to DBH; ATP7B is in cytoplasmic vesicles, where it sequesters Cu from the cytosol. Cu-bound DBH is located in secretory granules where it converts dopamine (DA) to norepinephrine (NE), which is then released upon neuronal activation. ( b ) Strategy for generating Atp7a ΔDbh and Atp7b ΔDbh mice: Atp7a LoxP/LoxP or Atp7b LoxP/LoxP female mice were crossed with male mice expressing Cre-recombinase under the DBH promoter ( DBH -Cre mice) for targeted deletion in noradrenergic neurons. ( c,d) Coronal brain sections from wild-type control and Atp7a ΔDbh (c) or Atp7b ΔDbh mice (d) were co-immunostained for tyrosine hydroxylase (Th) (Red), a marker of noradrenergic neurons, and either Atp7a (Green) or Atp7b (Green). In Atp7a ΔDbh and Atp7b ΔDbh mice, the respective transporter signal was undetectable in Th-positive neurons (outlined by dotted line), indicating successful deletion within the noradrenergic cell population. 3 coronal brain sections for n=3; animals were analyzed per genotype.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Activation Assay, Expressing, Control, Marker

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: (a) Analysis of Cu content in whole brain homogenates by atomic absorption spectroscopy found no difference for the age-matched 20-week-old wild-type, Atp7a ΔDbh , and Atp7b ΔDbh mice (b) Cu levels in peripheral tissues (liver, adipose) are unchanged across the genotypes. ( c ) Representative coronal brain sections analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) are shown, with metal distribution maps overlaid on tyrosine hydroxylase immunofluorescence confocal images (TH is green, nuclei are blue). Less intense Cu signal is apparent in the Th-positive region. ( d ) Quantitation of LA-ICP-MS signals in coronal brain sections reveals reduced Cu, Fe, and Zn levels in the locus coeruleus of Atp7a ΔDbh mice compared to wild-type controls. ( e ) Metal levels in the medulla oblongata (ROI) (indicated by white dotted lines) are compared across wild-type, Atp7a ΔDbh , and Atp7b ΔDbh mice. ( f ) Immunostaining for Atp7b (red) in noradrenergic LC neurons (TH, green; LC outlined by the white dotted line) shows reduced Atp7b signal in Atp7a ΔDbh mice compared to wild type ( g ) Immunostaining for Atp7a (red) in noradrenergic LC neurons (TH, green; LC outlined by white dotted line) shows no change in Atp7b ΔDbh mice compared to wild type. In all experiments, 3-4 mice were used for each genotype, ns = not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Atomic Absorption Spectroscopy, Clinical Proteomics, Mass Spectrometry, Immunofluorescence, Quantitation Assay, Immunostaining

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Metal maps for Cu, Zn, Fe and P on coronal brain sections from Wild type, Atp7a ΔDbh and Atp7b ΔDbh using LA-ICPMS

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques:

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: (a) Quantification of Atp7b fluorescent intensity in noradrenergic neurons of the Locus Coeruleus (LC), identified by TH staining, in Atp7a ΔDbh and Atp7aFlox coronal brain sections. n=3 animals were analyzed. Data were analyzed using GraphPad Prism 10 and are presented as mean ± SEM. Statistical significance was determined using an unpaired two-tailed Student’s t-test: p < 0.05, * p < 0.01, ** p < 0.001.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Staining, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: ( a ) Representative immunoblots of the whole-brain homogenates show markedly reduced Dbh expression in 20-week-old Atp7a ΔDbh compared to Atp7a LoxP/LoxP ( Atp7aFlox ) and wild-type controls. Additional replicates are shown in the . ( b ) Densitometry of DBH signal normalized to Na + /K + ATPase confirms significantly reduced Dbh in 20-week-old Atp7a ΔDbh brains. ( c ) Representative coronal brain sections (10 μm) from 20-week-old mice immunostained for Dbh (green) and tyrosine hydroxylase (Th, red) highlight noradrenergic neurons in the locus coeruleus (LC); Atp7a ΔDbh brains display marked loss of Dbh signal compared to controls. ( d ) Dbh-positive neurons were normalized to the total number of TH-stained neurons in the LC. Three coronal brain sections from n=3 animals per genotype were analyzed. ( e ) Immunoblots at 4 weeks similarly show reduced Dbh expression in both Atp7a ΔDbh and Atp7b ΔDbh . ( f ) Densitometry of the Dbh signal normalized to Na + /K + ATPase confirms significantly reduced Dbh in 4-week-old Atp7a ΔDbh and Atp7b ΔDbh brains. LC-MS metabolite analysis of whole-brain homogenates reveals a ( g ) decreased norepinephrine (NE) and ( h ) increased dopamine (DA)/NE ratio in Atp7a ΔDbh mice relative to Atp7aFlox controls (20 weeks, n=5). ( i ) increased DA/NE ratio in Atp7b ΔDbh brain homogenates relative to Atp7bFlox controls (20 weeks, n = 3). Data are mean ± SEM. Statistical analysis: unpaired two-tailed Student’s t-test with Welch’s correction; *p < 0.05, **p < 0.01. Data points for Atp7aFlox, Atp7bFlox, Atp7a ΔDbh , and Atp7b ΔDbh are shown in black, blue, orange, and green, respectively.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Western Blot, Expressing, Staining, Liquid Chromatography with Mass Spectroscopy, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Immunoblot showing (a) Dbh from the membrane fraction isolated from whole brain homogenate from Atp7aFlox (n = 4) and Atp7b ΔDbh (n=4) and Atp7bFlox (20 weeks) (b) Quantification of DBH normalized to Na+/K+ ATPase shows reduced expression in Atp7b ΔDbh compared to the Atp7bFlox controls. Statistical significance was determined using GraphPad Prism version 10 software using an unpaired Student’s t-test with Welch’s correction. * p < 0.05, ** p < 0.01, ns = not significant.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Western Blot, Membrane, Isolation, Expressing, Software

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Inactivating copper transporters in Dbh neurons affects brain and serum Norepinephrine levels. (a, b) LC–MS analysis of whole-brain homogenates shows no significant change in serotonin levels in Atp7a ΔDbh (a) or Atp7b ΔDb h (b) relative to LoxP/LoxP controls (20 weeks, n = 5). (c) Brain dopamine (DA) levels are significantly elevated in Atp7a ΔDbh mice compared to Atp7aFlox . Data are mean ± S.E.M. Statistical significance was determined using unpaired two-tailed Student’s t-test with Welch’s correction; *p < 0.05, **p < 0.01, *** p < 0.001.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Liquid Chromatography with Mass Spectroscopy, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: (a, b) Volcano plots showing differentially expressed proteins in Atp7a ΔDbh ( a ) and Atp7b ΔDbh ( b ) laser-dissected locus coeruleus compared to the respective LoxP/LoxP controls. (c, d) Principal component analysis of proteomic datasets demonstrates clear segregation between mutant and control samples for Atp7a ΔDbh ( c ) and Atp7b ΔDbh ( d ). ( e ) Immunofluorescence staining of coronal brain sections demonstrates accumulation of the autophagy adaptor p62 (red) in Atp7a ΔDbh neurons, colocalizing with tyrosine hydroxylase (TH, green). (f) Enhanced microglial activation in Atp7a ΔDbh LC, indicated by increased Iba1 immunoreactivity (red). ( g ) Iba1 staining in Atp7b ΔDbh LC is similar to controls. ( h ) Quantification of Iba1+ cells in the LC (n = 3 mice per genotype). Data are mean ± SEM. Statistical analysis: unpaired two-tailed Student’s t-test with Welch’s correction; *p < 0.05, **p < 0.01. Data points for Atp7aFlox , Atp7bFlox , Atp7a ΔDbh , and Atp7b ΔDbh are shown in black, blue, orange, and green, respectively.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Mutagenesis, Control, Immunofluorescence, Staining, Activation Assay, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Immunostaining for SNCA (red) in Atp7b ΔDbh shows upregulation of SNCA in TH+ve (green) noradrenergic neurons in the LC region compared to the Atp7bFlox controls (20 weeks)

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Immunostaining

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Conditional inactivation of Atp7a in Dbh neurons disrupts systemic energy metabolism. Whole-body metabolic parameters were measured in wild-type (black), Atp7a ΔDbh , and Atp7b ΔDbh male mice using the Comprehensive Lab Animal Monitoring System (CLAMS; Columbus Instruments) over a continuous 48-h recording period following 24 h acclimatization. (a) Oxygen consumption (VO₂) and (b) carbon dioxide production (VCO₂) normalized to either lean mass or body weight. (c) Respiratory exchange ratio (RER). Light and dark phases are indicated, and whole-day averages are shown. Data represent mean ± SEM, with individual animals shown as dots. Statistical analyses were performed using two-way ANOVA followed by Tukey’s multiple comparison test; *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Comparison

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: (a) Images illustrating the warmth-seeking behaviour of Atp7a ΔDbh and Atp7b ΔDbh mice compared to the Atp7aFlox and Atp7bFlox animals. ( b ) Hematoxylin and eosin (H&E)-stained sections of brown adipose tissue (BAT) show enlarged adipocytes in Atp7a ΔDbh and Atp7b ΔDbh mice relative to the wild type. (c) Quantification of BAT adipocyte size confirms a significant increase in adipocyte size in both mutants. (d–e) Relative mRNA expression of thermogenesis-related genes in BAT: ( d ) PGC1α and ( e ) UCP1 are reduced in Atp7a ΔDbh compared to wild type. ( f ) H&E-stained sections of inguinal white adipose tissue (iWAT) reveal enlarged adipocytes in Atp7a ΔDbh . ( g ) Quantification of iWAT adipocyte size demonstrates significantly increased adipocyte size in Atp7a ΔDbh mice compared to wild type. (h) H&E-stained sections of gonadal white adipose tissue (gWAT). ( i ) Quantification of gWAT adipocyte size shows significantly increased adipocyte size in Atp7a ΔDbh mice compared to wild type. Data represent mean ± SEM. Statistical analysis: unpaired Student’s t-test; ns = not significant; *p < 0.05, **p < 0.01, ****p < 0.0001.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Staining, Expressing

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: Weight of adipose tissues isolated from mice kept at room temperature (22-24⁰ C) (a) BAT from Atp7a ΔDbh animals shows significantly increased weight compared to the Wild type (20 weeks). Atp7b ΔDbh did not show any significant change (b) iWAT (c) gWAT did not reveal any significant difference in adipose tissue weight in mutants compared to the wild type controls. Data were represented as Mean ± SEM. Statistical significance was determined using GraphPad Prism version 10 software using an unpaired Student’s t-test with Welch’s correction. *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Isolation, Software

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: (a) Immunohistochemistry for UCP1 of adipose tissues, such as BAT, gWAT and iWAT shows intense DAB staining in Atp7aFlox animals while Atp7a ΔDbh shows minimal staining suggesting reduced expression of UCP1 following acute cold stress; n=3. (b, c) Atp7a ΔDbh mice (n=5) show reduced PGC1α and UCP1 mRNA expression in BAT compared to Atp7aFlox mice (n=4) normalized to GAPDH mRNA expression. (e) Immunohistochemistry for UCP1 of adipose tissues, such as BAT, gWAT and iWAT shows intense DAB staining in Atp7bFlox animals while Atp7b ΔDbh shows minimal staining suggesting reduced expression of UCP1 following cold exposure; n=3). Statistical significance was determined using Graphpad Prism Version 9, using an unpaired two-tailed Student’s t -test with Welch correction; P < 0.05, P < 0.01.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Immunohistochemistry, Staining, Expressing, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet: ( a ) Twelve-week-old male Atp7b ΔDbh and Atp7bFlox animals (n = 4 per genotype) were exposed to cold exposure (6°C) for 6 hours and showed a mild thermoregulatory defect. Although partial recovery was observed at 6 hours in both groups, Atp7b ΔDbh mice continued to trend toward hypothermia compared to Atp7bFlox controls. ( b ) The body weight of Atp7b ΔDbh and Atp7bFlox controls remained unchanged before and after cold exposure. ( c ) Atp7b ΔDbh animals displayed significantly increased BAT weight relative to controls. ( d, e ) gWAT and iWAT weights showed no significant difference between Atp7b ΔDbh and Atp7bFlox controls. ( f ) Representative H&E-stained BAT sections from Atp7aFlox and Atp7a ΔDbh mice following cold stress at 6°C for 6 hours revealed enlarged adipocytes in Atp7a ΔDbh animals, consistent with impaired lipolysis. ( g ) Quantification confirms significant increases in adipocyte size in BAT in Atp7a ΔDbh animals compared to the Atp7bFlox controls. Data are shown as mean ± SEM ( n = 4 mice per group). Statistical significance was determined using Graphpad Prism Version 10, using an unpaired two-tailed Student’s t -test with Welch’s correction. * p < 0.05, **p < 0.01, ****p < 0.0001; ns = not significant.

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques: Staining, Two Tailed Test

Journal: bioRxiv

Article Title: NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

doi: 10.64898/2026.01.15.699802

Figure Lengend Snippet:

Article Snippet: To generate mice with a targeted deletion of Atp7a or Atp7b in noradrenergic cells, female Atp7a LoxP/LoxP or Atp7b LoxP/LoxP animals were crossed with males expressing Cre recombinase under the control of the dopamine β-hydroxylase ( Dbh ) promoter (Dbh-Cre; Jackson Laboratory strain B6.Cg- Dbh tm3.2(cre)Pjen /J).

Techniques:

Journal: Chemical & Biomedical Imaging

Article Title: An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems

doi: 10.1021/cbmi.5c00237

Figure Lengend Snippet: Copper-based nanoparticle internalization affects the regulation of cellular copper ion flux. (a) Western Blot analysis of ATP7B, CTR1, and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) proteins in A549 cells treated with 6.25 μg Cu·mL –1 Cu–oxide, 3.125 μg Cu·mL –1 Cu–HCF, or vehicle control for 1 or 24 h. Quantified (b) CTR1 and (c) ATP7b expression after incubation with Cu–oxide or Cu–HCF for 1 or 24 h. Error bars denote SEM. Full gel images are posted in the Supporting Information .

Article Snippet: ATP7B antibody was purchased from Novus Biological (NB100–360) and used with a dilution of 1:1000.

Techniques: Western Blot, Control, Expressing, Incubation

Journal: Chemical & Biomedical Imaging

Article Title: An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems

doi: 10.1021/cbmi.5c00237

Figure Lengend Snippet: Schematic depiction of a model showing the effects of copper-based nanoparticles on copper homeostasis and compensatory biochemical responses in cells. (a) A basal, physiological scenario where copper and intracellular redox status are under normal and regulated homeostatic control. (b) A high-copper perturbation scenario following nanoparticle internalization and copper ion leaching where a significant pool of labile Cu­(II) is generated. To overcome this acute or chronic aberrant exposure to excess of this metal and accompanying oxidative stress, cells sequester excess copper via GSH and NRF2 antioxidant pathways with concomitant upregulation of the copper ion export protein ATP7B to promote copper efflux and downregulation of the copper ion import protein CTR1 to block copper influx.

Article Snippet: ATP7B antibody was purchased from Novus Biological (NB100–360) and used with a dilution of 1:1000.

Techniques: Control, Generated, Blocking Assay