Clioquinol changes the expression profiles and redox states of proteins involved in copper/zinc homeostasis

Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.

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Copper-To-Zinc Ratio as an Inflammatory Marker in Patients with Sickle Cell Disease

Sci ◽

10.3390/sci2040089 ◽

2020 ◽

Vol 2 (4) ◽

pp. 89

Author(s):

Mathias Abiodun Emokpae ◽

Emmanuel Bamidele Fatimehin

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Serum Levels ◽

Serum Copper ◽

The Body ◽

Zinc Homeostasis ◽

Clinical State ◽

Cell Disease ◽

Copper And Zinc ◽

Copper Zinc

Sickle cell disease (SCD) is an inherited disorder and a major health challenge in Nigeria. Micronutrient deficiencies often associated with the disorder may cause inflammation and abnormal metabolism in the body. The copper-to-zinc ratio is a more relevant diagnostic measure than the concentration of either metal alone in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and the copper-to-zinc ratio, and to correlate the latter with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age- and sex-matched subjects with normal hemoglobin. Serum copper and zinc were assayed by the colorimetric method using reagents supplied by Centronic, Germany, while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper-to-zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using the Students t-test, and the Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and the copper-to-zinc ratio were significantly higher (p < 0.001), while zinc level was lower in SCD patients than in controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and the copper-to-zinc ratio (r = 0.312; p < 0.002), but the correlation between CRP and fibrinogen was not significant. Inflammation may modulate copper and zinc homeostasis, and the copper-to-zinc ratio may be used as a marker of nutritional deficiency and inflammation in SCD patients.

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Efficacy of Microencapsulated Probiotic as Adjunct Therapy on Resolution of Diarrhea, Copper-Zinc Homeostasis, Immunoglobulins, and Inflammatory Markers in Serum of Spontaneous Rotavirus-Infected Diarrhoetic Calves

Probiotics and Antimicrobial Proteins ◽

10.1007/s12602-021-09862-9 ◽

2021 ◽

Author(s):

Jitendra Singh Gandhar ◽

Ujjwal Kumar De ◽

Anju Kala ◽

Yashpal Singh Malik ◽

Supriya Yadav ◽

...

Keyword(s):

Inflammatory Markers ◽

Zinc Homeostasis ◽

Adjunct Therapy ◽

Copper Zinc

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Copper-to-Zinc Ratio Correlates with an Inflammatory Marker in Patients with Sickle Cell Disease (Version 1)

Sci ◽

10.3390/sci1020034 ◽

2019 ◽

Vol 1 (2) ◽

pp. 34

Author(s):

Mathias Abiodun Emokpae ◽

Emmanuel Babatunde Fatimehin

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Serum Levels ◽

Serum Copper ◽

The Body ◽

Zinc Homeostasis ◽

Clinical State ◽

Cell Disease ◽

Copper And Zinc ◽

Copper Zinc

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

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Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome

Physiological Genomics ◽

10.1152/physiolgenomics.00024.2007 ◽

2007 ◽

Vol 30 (2) ◽

pp. 146-155 ◽

Cited By ~ 154

Author(s):

Hector R. Wong ◽

Thomas P. Shanley ◽

Bhuvaneswari Sakthivel ◽

Natalie Cvijanovich ◽

Richard Lin ◽

...

Keyword(s):

Septic Shock ◽

Expression Profiles ◽

Serum Zinc ◽

Zinc Homeostasis ◽

Biologically Relevant ◽

Gene Probes ◽

Canonical Pathways ◽

Genome Level ◽

Zinc Levels ◽

Gene Ontologies

Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock ( n = 42) and controls ( n = 15). Both gene lists encompassed several biologically relevant gene ontologies and canonical pathways. Notably, many of the genes downregulated in the patients with septic shock, relative to the controls, participate in gene ontologies related to metal or zinc homeostasis. Comparison of septic shock survivors ( n = 33) and nonsurvivors ( n = 9) demonstrated differential regulation of 63 gene probes. Among the 63 gene probes differentially regulated between septic shock survivors and nonsurvivors, two isoforms of metallothionein (MT) demonstrated increased expression in the nonsurvivors. Consistent with the ability of MT to sequester zinc in the intracellular compartment, nonsurvivors had lower serum zinc levels compared with survivors. In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice. These data represent the largest reported cohort of pediatric patients with septic shock that has undergone genome-level expression profiling based on microarray. The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock.

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Copper-to-Zinc Ratio Correlates with an Inflammatory Marker in Patients with Sickle Cell Disease

Sci ◽

10.3390/sci1020055 ◽

2019 ◽

Vol 1 (2) ◽

pp. 55

Author(s):

Mathias Abiodun Emokpae ◽

Emmanuel Bamidele Fatimehin

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Serum Levels ◽

Serum Copper ◽

The Body ◽

Zinc Homeostasis ◽

Clinical State ◽

Cell Disease ◽

Copper And Zinc ◽

Copper Zinc

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

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Alterations of hemogram, serum biochemistry, oxidative/nitrosative balance, and copper/zinc homeostasis in dromedary camels naturally infected with poxvirus

Tropical Animal Health and Production ◽

10.1007/s11250-020-02318-2 ◽

2020 ◽

Vol 52 (6) ◽

pp. 2997-3003

Author(s):

U. K. De ◽

V. Chander ◽

Akhilesh ◽

S. Mahajan ◽

G. K. Sharma ◽

...

Keyword(s):

Serum Biochemistry ◽

Zinc Homeostasis ◽

Dromedary Camels ◽

Copper Zinc

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Maternal protein restriction affects gene expression profiles in the kidney at weaning with implications for the regulation of renal function and lifespan

Clinical Science ◽

10.1042/cs20100230 ◽

2010 ◽

Vol 119 (9) ◽

pp. 373-387 ◽

Cited By ~ 18

Author(s):

Jian-Hua Chen ◽

Jane L. Tarry-Adkins ◽

Kieran Matharu ◽

Giles S. H. Yeo ◽

Susan E. Ozanne

Keyword(s):

Gene Expression ◽

Cellular Senescence ◽

Low Birthweight ◽

Expression Profiles ◽

Adult Life ◽

Gene Expression Profiles ◽

Protein Restriction ◽

Copper Zinc Superoxide Dismutase ◽

Maternal Protein Restriction ◽

Copper Zinc

Nutritionally induced alterations in early growth can influence health and disease in later adult life. We have demonstrated previously that low birthweight resulting from maternal protein restriction during pregnancy followed by accelerated growth in rodents was associated with shortened lifespan, whereas protein restriction and slow growth during lactation increased lifespan. Thus early life events can also have a long lasting impact on longevity. In the present study, we show that long-lived PLP (postnatal low protein) mice were protected from developing albuminuria, whereas short-lived recuperated mice demonstrated an age-dependent increase in albuminuria in old age. Microarray analysis of kidneys from 21-day-old mice revealed that gene expression profiles were differentially affected depending on whether protein restriction was imposed during pregnancy or lactation. The differentially expressed genes were involved in diverse biological functions such as cytoprotective functions, vitamin D synthesis, protein homoeostasis, regulation of antioxidant enzymes and cellular senescence. Significantly, up-regulation of Hmox1 (haem oxygenase 1) in kidneys from PLP mice suggests that tissues of long-lived mice are equipped with a better cytoprotective function. In contrast, up-regulation of Nuak2 (NUAK family, SNF1-like kinase 2) and down-regulation of Lonp2 (Lon peptidase 2), Foxo3a (forkhead box O3a), Sod1 (copper/zinc superoxide dismutase) and Sesn1 (sestrin 1) in the kidneys of recuperated offspring suggest that protein homoeostasis and resistance to oxidative stress are compromised, leading to accelerated cellular senescence in these shorter-lived mice.

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Effects of Essential Oils from Cymbopogon spp. and Cinnamomum verum on Biofilm and Virulence Properties of Escherichia coli O157:H7

Antibiotics ◽

10.3390/antibiotics10020113 ◽

2021 ◽

Vol 10 (2) ◽

pp. 113 ◽

Cited By ~ 1

Author(s):

Raffaella Scotti ◽

Annarita Stringaro ◽

Laura Nicolini ◽

Miriam Zanellato ◽

Priscilla Boccia ◽

...

Keyword(s):

Escherichia Coli ◽

Essential Oils ◽

Biofilm Formation ◽

Expression Profiles ◽

Enterohemorrhagic Escherichia Coli ◽

Zinc Homeostasis ◽

Transcriptional Analysis ◽

Escherichia Coli O157 ◽

Biofilm Inhibition ◽

E Coli

Every year, the pharmaceutical and food industries produce over 1000 tons of essential oils (EOs) exploitable in different fields as the development of eco-friendly and safe antimicrobial inhibitors. In this work we investigated the potential of some EOs, namely Cinnamomum verum, Cymbopogon martini, Cymbopogoncitratus and Cymbopogon flexuosus, on the growth, biofilm formation and gene expression in four strains of enterohemorrhagic Escherichia coli O157:H7. All EOs were analyzed by gas chromatography-mass spectrometry (GC-MS). The antimicrobial activity was performed by using dilutions of EOs ranging from 0.001 to 1.2% (v/v). Subinhibitory doses were used for biofilm inhibition assay. The expression profiles were obtained by RT-PCR. E. coli O157:H7 virulence was evaluated in vivo in the nematode Caenorhabditis elegans. All EOs showed minimal inhibitory concentrations (MICs) ranging from 0.0075 to 0.3% (v/v). Cinnamomum verum bark EO had the best activity (MIC of 0.0075% (v/v) in all strains) while the C. verum leaf EO had an intermediate efficacy with MIC of 0.175% (v/v) in almost all strains. The Cymbopogon spp. showed the more variable MICs (ranging from 0.075 to 0.3% (v/v)) depending on the strain used. Transcriptional analysis showed that C. martini EO repressed several genes involved in biofilm formation, virulence, zinc homeostasis and encoding some membrane proteins. All EOs affected zinc homeostasis, reducing ykgM and zinT expression, and reduced the ability of E. coli O157:H7 to infect the nematode C. elegans. In conclusion, we demonstrated that these EOs, affecting E. coli O157:H7 infectivity, have a great potential to be used against infections caused by microorganisms.

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