Ceruloplasmin Deficiency Impaired Brain Iron Metabolism and Behavior in Mice

February 21, 2022 0 Comments

Iron accumulation is an important cause of various brain diseases. As a ferroxidase, ceruloplasmin (Cp) plays a key role in iron homeostasis and its abnormal activity leads to iron accumulation. However, the detailed biological function of Cp in brain iron homeostasis needs to be investigated. In this study, Cp knockout mice were prepared and the changes in iron content and protein expression related to iron metabolism were detected. The results showed that iron accumulation occurred in multiple tissues and organs of Cp knockout mice, but there was no obvious change in brain tissues.
However, Cp deficiency affected the expression of many iron metabolism-related proteins in midbrain, such as DMT1+IRE, heavy chain ferritin (H-ferritin) and light chain ferritin (L-ferritin). Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. In vitro cell experiment indicated that the sensitivity of Cp knockout neuron and astrocyte to hypoxia was higher than that of wild type, which means Cp deficiency leads to the damage of cell self-protection. All these results confirm that Cp exerts a protective effect on the brain by regulating iron metabolism.

Sensitive New Assay System for Serum Wisteria floribunda Agglutinin-Reactive Ceruloplasmin That Distinguishes Ovarian Clear Cell Carcinoma from Endometrioma

Wisteria floribunda agglutinin (WFA)-reactive ceruloplasmin (CP) is a candidate marker for ovarian clear cell carcinoma (CCC) reported in our previous paper. Herein, a new measurement system was developed to investigate its potential as a serum marker for CCC. Site-specific glycome analysis using liquid chromatography/mass spectrometry showed that WFA-CP from CCC binds to WFA via the GalNAcβ1,4GlcNAc (LDN) structure. We used mutant recombinant WFA (rWFA), which has a high specificity to the LDN structure, instead of native WFA, to increase the specificity of the serum sample measurement.
To improve the sensitivity, we used a surface plasmon field-enhanced fluorescence spectroscopy immunoassay system, which is approximately 100 times more sensitive than the conventional sandwich enzyme-linked immunosorbent assay system. With these two improvements, the specificity and sensitivity of the serum rWFA-CP measurement were dramatically improved, clearly distinguishing CCC from endometrioma, from which CCC originates. This rWFA-CP assay can be used clinically for the serodiagnosis of early-stage CCC, which is difficult to detect with existing serum markers
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Iron Deficiency in Inflammatory Bowel Disease Is Associated With Low Levels of Vitamin D Modulating Serum Hepcidin and Intestinal Ceruloplasmin Expression

Introduction: Iron deficiency and vitamin D deficiency are common comorbidities in inflammatory bowel disease (IBD). Accumulating evidence indicates that active 1,25-dihydroxyvitamin D (1,25(OH)D) may enhance iron absorption by suppressing hepcidin. We investigated the influence of vitamin D on iron metabolism in patients with IBD and on the expression of genes facilitating intestinal epithelial iron absorption.
Methods: Iron parameters and serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25(OH)D, and hepcidin were measured in 104 adult patients with IBD (67 with Crohn’s disease and 37 with ulcerative colitis). Genes involved in iron absorption were tested for induction by 1,25(OH)D in Caco-2 cells, which resemble the small intestinal epithelium.
Results: In multiple regression models controlling for age, sex, body mass index, smoking status, disease activity, and C-reactive protein levels, low 25(OH)D levels were associated with iron deficiency in patients with IBD (β [SE] = -0.064 [0.030], P = 0.029). Vitamin D sufficiency was associated with increased levels of ferritin (β [SE] = 0.25 [0.11], P = 0.024) and transferrin saturation (β [SE] = 8.41 [4.07], P = 0.044). Higher 1,25(OH)D:25(OH)D ratios were associated with lower hepcidin levels (β [SE] = -4.31 [1.67], P = 0.012). Especially in Crohn’s disease, increased 1,25(OH)D correlated with higher transferrin saturation (β [SE] = 0.43 [0.18], P = 0.027). Furthermore, 1,25(OH)D strongly induced the expression of the ferroxidase ceruloplasmin in Caco-2 cells.
Discussion: Low vitamin D levels in IBD correlate with iron deficiency. Vitamin D may ameliorate iron deficiency, potentially by downregulating hepcidin and upregulating ceruloplasmin, enhancing intestinal iron absorption.

Assessment of Serum Selenium and Ceruloplasmin in Potentially Malignant Disorders and Oral Cancer

Introduction: Despite extensive research and development, potentially malignant disorders (PMDs) of the oral cavity and oral cancer remain a serious concern. Diet and immunity have been identified as important modifiable factors in such diseases.
Materials and methods: A total of 20 patients and 10 healthy individuals, aged 30-60 years, were chosen from the outpatient Department of Oral and Maxillofacial Surgery, Yenepoya Dental College and hospital, Karnataka. The participants were grouped into three: Group 1: (10 healthy individuals), Group 2: (10 oral leukoplakia patients) and Group 3: (10 squamous cell carcinoma patients). Blood was chosen as the investigative medium. Ceruloplasmin was estimated by the diamine oxidase method. The technique of atomic absorption developed by Sir Alan Walsh in 1950 has become the preferred method of elemental analysis of selenium (atomic absorption spectrometer). Statistical analysis of the data obtained was done using one-way ANOVA test and the Turkey multiple comparisons test.
Results: The intergroup comparison of ceruloplasmin shows that the mean value of Group I (Control) was 31.746 mg/dl, the mean value of Group II (leukoplakia) was 81.411 mg/dl, and the mean value of Group III (squamous cell carcinoma) was 90.7120 mg/dl. The intergroup comparison of selenium levels shows that the mean value of Group I (Control) was 119.937 (ng/ml), the mean value of Group II (leukoplakia) was 109.17 (ng/ml), and the mean value of Group III (squamous cell carcinoma) was 99.6230 (ng/ml).
Conclusion: Antioxidants are an important defense system against free radical damage to cells. Ceruloplasmin and selenium levels in serum could be used as disease markers in leukoplakia and squamous cell carcinoma.


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Serum copper, ceruloplasmin, and their relations to metabolic factors in nonalcoholic fatty liver disease: a cross-sectional study

Objective: Nonalcoholic fatty liver disease (NAFLD) characterized by excessive intrahepatic fat accumulation is increasing worldwide. This study aimed to investigate serum copper (Cu) and ceruloplasmin (Cer) levels and their relations to metabolic factors in NAFLD.
Methods: This cross-sectional study was conducted on 141 subjects with NAFLD diagnosed using abdominal ultrasonography. Personal information, anthropometric measures, glucose and lipid profile, and serum levels of liver enzymes were assessed. Fasting serum levels of Cu and Cer were determined using colorimetry and nephelometry assay, respectively. Odds ratios (ORs) were used to examine the associations of serum Cu and Cer levels with NAFLD risk.
Results: The results on 85 patients with NAFLD and 56 apparently healthy participants showed that all NAFLD cases and 53.6% of the healthy subjects were overweight or obese. More than half of the patients (58.8%) showed mild NAFLD. Age, weight, BMI, lipid profile, uric acid, and ferritin were significantly higher in NAFLD patients than the healthy cases. No significant differences were found in the concentrations of Cu and Cer between the groups. Only 7.4% of the healthy subjects and 2.4% of the patients were Cu deficient (<70 µg/dl). No association was found between the risk of NAFLD and serum Cu [OR: 0.994; 95% confidence interval (CI): 0.981-1.006] and Cer levels (OR: 0.414; 95% CI: 0.001-123.604) after adjusting for the confounders.
Conclusion: Our findings revealed no association between Cu deficiency and NAFLD risk. Further human studies with larger sample sizes are required to investigate how Cu and Cer status may affect NAFLD.

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