Correlation between molecular heterogeneity of ceruloplasmin mRNA and ceruloplasmin isomers synthesized in rat liver

Molecular heterogeneity of ceruloplasmin mRNA is studied in rat liver polyribosomes. Blot hybridization of RNA with cDNA reveals three molecular forms of ceruloplasmin mRNA differing in the chain length and structure of the 3′-regions. A correlation between these mRNAs and three isoforms of ceruloplasmin, which perform different functions in the copper transport, is established. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 79–82, January, 1997     

Iron homeostasis in astrocytes and microglia is differentially regulated by TNF-α and TGF-β1

Abnormal iron homeostasis is increasingly thought to contribute to the pathogenesis of several neurodegenerative disorders. We have previously reported impaired iron homeostasis in a mouse model of spinal cord injury and in a mouse model of amyotrophic lateral sclerosis. Both these disorders are associated with CNS inflammation. However, what effect inflammation, and in particular, inflammatory cytokines have on iron homeostasis in CNS glia remains largely unknown. Here we report that the proinflammatory cytokine TNF-α, and the anti-inflammatory cytokine TGF-β1 affect iron homeostasis in astrocytes and microglia in distinct ways. Treatment of astrocytes in vitro with TNF-α induced the expression of the iron importer "divalent iron transporter 1" (DMT1) and suppressed the expression of the iron exporter ferroportin (FPN). However, TGF-β1 had no effect on DMT1 expression but increased the expression of FPN in astrocytes. In microglia, on the other hand, both cytokines caused induction of DMT1 and suppression of FPN expression. Iron influx and efflux assays in vitro confirmed that iron homeostasis in astrocytes and microglia is differentially regulated by these cytokines. In particular, TNF-α caused an increase in iron uptake and retention by both astrocytes and microglia, while TGF-β1 promoted iron efflux from astrocytes but caused iron retention in microglia. These data suggest that these two cytokines, which are expressed in CNS inflammation in injury and disease, can have profound and divergent effects on iron homeostasis in astrocytes and microglia.     

COPPER TOXICITY, RATS AND WILSON'S DISEASE

The ability to store ionic copper in tissues such as the liver and the brain may be one of the main causes of copper accumulation in these organs of patients with Wilson's disease. In rats drinking water high in copper, the organs which can take up ionic copper store it and they are not protected from copper toxicity. On the other hand, those organs which require copper bound in ceruloplasmin for storage, do not show excess copper and thus, are protected from copper toxicity.     

铜蓝蛋白基因在矽肺肺组织中的表达

为探明矽肺病变过程中是否存在肝外铜蓝蛋白（ｃｅｒｕｌｏｐｌａｓｍｉｎ，Ｃｐ）ｍＲＮＡ表达，我们采用分子杂交手段包括斑点杂交、原位杂交以及ＮｏｒｔｈｅｒｎＢｌｏｔｉｎｇ印迹法对染尘２１天大鼠肺组织及肺泡巨噬细胞（ＡＭ）进行系列分析。结果表明：肺组织有ＣｐｍＲＮＡ的表达，与生理盐水对照组相比，矽肺组肺组织ＣｐｍＲＮＡ表达水平增高约２倍。原位杂交结果显示矽肺组织内肺间质细胞和肺泡巨噬细胞均有阳性杂交颗粒，ＮｏｒｔｈｅｒｎＢｌｏｔｉｎｇ印迹杂交进一步证实ＡＭ中存在ＣｐｍＲＮＡ表达。矽肺过程中，肺组织是主要的肝外ＣｐｍＲＮＡ表达器官之一。提示Ｃｐ可能在肺组织损伤和修复过程中起重要作用     

COPPER METABOLISM IN PATIENTS WITH LIVER DISEASE

Kayser-Fleischer rings have been described in liver disease states other than Wilson's disease, primarily in patients with primary biliary cirrhosis (PBC). In patients with PBC, hepatic copper, serum copper, urine copper and serum ceruloplasmin concentrations are significantly elevated. In Wilson's disease, excessive copper release from liver cells can cause intravascular hemolysis.     

Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters

The study was designed to investigate the possible correlation between some oxidative stress parameters in Behcet's disease and the clinical manifestations of the disease as well as the possible correlation with the disease severity. Seventy-six patients diagnosed according to the International Study Group criteria for Behcet's disease were included in the study. Sixty patients had mild-to-moderate disease and 16 patients had severe disease. Sixty matched control subjects were also included. After a full history and examination from each subject, 10 mL blood was drawn from each for analysis. Serum malondialdehyde, glutathione, ceruloplasmin, copper and zinc levels were determined. Patients with Behcet's disease showed increased levels of serum malondialdehyde and copper while glutathione and zinc levels were decreased. Comparison between these parameters in patients with mild-to-moderate disease with those with severe disease showed only that serum zinc levels were lower in severe Behcet's disease. Serum malondialdehyde levels were found to be significantly positively correlated with oral ulcer size, duration and frequency. Glutathione levels were found to be inversely correlated with the clinical manifestation index and all oral ulcer parameters. Zinc levels were found to be inversely correlated with the clinical manifestation index and pathergy test positivity grades. Copper levels were found to be positively correlated with oral ulcer number. Although the parameters of oxidative stress did not show correlation with disease severity, they were correlated with the disease manifestations. This points out the importance of oxidative stress in Behcet's disease.     

Evidence that human ceruloplasmin molecule consists of homologous parts

The products of spontaneous and induced proteolysis of human ceruloplasmin (Cp) were studied. Some physico-chemical properties of the six fragments with electrophoretically determined Mr 13 0000 (F₁), 110000 (F₂), 66 000 (F₃), 48 000 (F₄) 22 000 (F₅) and 18 000 (F₆) were compared. The amino acid compositions and N-terminal amino acid sequences coincide in F₁–F₅, but differ from those of F₆. Limited tryptic proteolysis of Cp causes the accumulation of polypeptide fragment with Mr 22 000, the N-terminal primary structure of which is identical to that of F₅ produced by spontaneous proteolysis. Electrophoretic fragments of Cp were extracted from polyacrylamide gel, treated with ¹²⁵I and then studied by peptide mapping with subsequent radioautography. The comparison of the “finger prints” showed the identity of F₁ to F₂ and F₃ and gross similarity between F₄ and F₁– F₃. It also revealed similar peptides in F₅ and F₆ hydrolyzates and almost perfect matching of the F₄ map to the map of F₅+ F₆ mixture. On the basis of the obtained data general principles of Cp molecular organization are discussed and intramolecular homology is suggested to be a feature of the protein.     

Interaction of ceruloplasmin with the plasma membrane receptors of CV-1 cells and its feedback regulation

It is shown that cultured cells of the CV-1 line possess the capacity for high-affinity binding of ceruloplasmin, show a kinetics of saturation, and internalize ceruloplasmin. Propagation of cells in medium supplemented with fetal calf serum depleted of ceruloplasmin results in a two-fold increase of high-affinity receptor expression on the cell surface. This phenomenon is not accompanied by any change in the receptor-ligand affinity. Ceruloplasmin binding to the cell surface and subsequent internalization do not lead to its marked degradation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 4, pp. 417–420, April, 1995 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences     

COPPER METABOLISM IN PREMATURE AND LOW-BIRTH-WEIGHT NEONATES

Copper deficiency syndrome appears to be more common in premature infants. The circulating levels of copper in neonates, however, appear to be controlled by hepatic maturity, and are resistant to dietary supplementation with copper.