Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The body's protective responses to infection, wounding, trauma, and malignancy include the acute-phase reaction, which is modulated by various cytokines and their cellular receptors. During the acute-phase reaction, levels of specific proteins synthesized by the liver increase in the plasma. Little information is available about the extrahepatic synthesis of plasma proteins during the acute-phase reaction. The study described here analyzes the tissue-specific expression of genes encoding the plasma proteins albumin (ALB), alpha 1-antitrypsin (AAT), transferrin (TF), haptoglobin (HP), ceruloplasmin (CP), serum amyloid A (SAA), alpha 1-acid glycoprotein (AGP) and alpha 2-HS-glycoprotein (AHSG) during the acute-phase reaction in C57B1 mice. The acute-phase reaction was induced by intraperitoneal injections of bacterial lipopolysaccharide (LPS). During the acute-phase reaction, genes encoding CP, SAA, AGP, and HP demonstrate unique extrahepatic tissue specific patterns of expression in kidney, spleen, thymus, heart, brain, lung, testis, and epididymis. Different temporal patterns of HP gene expression also were observed in lung and thymus after induction by LPS. The function of extrahepatic synthesis of plasma proteins is not yet understood; however, a local provision of specific plasma proteins in mammalian tissues may offer the host a source of functionally important proteins during periods of stress.
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PMID:Extrahepatic expression of plasma protein genes during inflammation. 175 24

As was stated in the introduction, many of the functions of the Sertoli cells are apparently carried out by the protein secretions of these cells. The use of Sertoli cell cultures and appropriate biochemical and immunological techniques has allowed the characterization of some of these secretion products. It is likely that many of the functions of the Sertoli cells are necessary because of the presence of the blood-testis barrier. Many growth and nutritive factors which are necessary for cell viability are available to most cells via the serum. The germinal cells within the adluminal compartment do not have access to serum factors and one of the functions of the Sertoli cells is to synthesize serum-like components and secrete them into the adluminal compartment. The historical description of Sertoli cells as "nurse cells" thus appears to have been accurate. The nurse-cell function is most clearly demonstrated by the proposed mechanism by which germinal cells obtain ferric ions. The Sertoli cells have developed a system to move serum-derived iron through their own cytoplasm and to secrete it bound to newly synthesized testicular transferrin molecules which can deliver it to specific receptors on the germinal cell surface (Huggenvik et al., 1984). Functionally, all of the secreted proteins from Sertoli cells which have been characterized or proposed fall into one of five basic classes. First, Sertoli cells secrete a number of transport proteins including transferrin, ceruloplasmin, and ABP. The proposed function of these proteins is the transport of Fe3+, Cu2+, and androgens to the germinal cells or to the epididymis (ABP). Second, Sertoli cells synthesize and secrete a number of proteins which have a hormone-like or growth factor-like activity. AMH is a clear and well-documented example of this type of product while the evidence for inhibin, somatomedin C, EGF-like growth factor, and seminiferous growth factor will require further corroboration. Third, Sertoli cells secrete proteins which have enzymatic activities. Plasminogen activator is the best characterized example of this class of products and the alpha-lactalbumin-like activity is of potential interest. The fourth class of Sertoli cell secretion products includes those proteins which contribute to the basement membrane, namely, type IV collagen and laminin. Finally, there is a very important group of Sertoli cell secretion products for which there is, as yet, no evidence for a defined function. This group includes SGP-1 and SGP-2 which are the major sertoli cell products in rats and which have been well-characterized biochemically.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protein secretions of Sertoli cells. 305 98

Based on its ability to chelate copper, TTM is being studied as an antiangiogenic agent for cancer therapy. The purpose of this study was to evaluate the toxicity of TTM and the protection of copper supplementation on the reproductive capability of male and female CD rats. Doses of 0, 1, 4, and 12 mg/kg/day with copper supplementation (110 mg/kg of diet) were given by gavage. There were no effects on the estrous cycle or reproductive indices, or maternal toxicity in any female dose group. Male rats given 12 mg/kg/day showed significant decreases in body weight gains and food consumption, and anemia. Serum ceruloplasmin levels were dose-dependently decreased in all male dose groups. Reduced epididymal weights, sperm counts, and sperm motility, sperm morphologic abnormalities and histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day. Dietary copper supplementation prevented the adverse sperm effects produced by 12 mg/kg/day of TTM.
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PMID:The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats. 1550 88

Copper (Cu) is an essential trace element required for the normal development of living organisms. Due to its redox potential, copper is a cofactor in many enzymes responsible for important processes in cells. Copper deficiency has a significant influence on the reduction or the total eradication of copper-dependent enzymes in the body, thereby inhibiting cell life processes. On the other hand, copper is a very reactive element and in its free state, it can trigger the production of large amounts of free radicals, which will consequently lead to the damage of proteins and DNA. Because of those reasons, living organisms have developed precise mechanisms regulating the concentration of copper in cells. Copper also plays a very important role in male fertility. It is an essential element for the production of male gametes. The significant role of copper is also described in the processes of cell division - mitotic and meiotic. Copper-dependent enzymes such as ceruloplasmin, superoxide dismutase SOD1 and SOD3, group of metallothionein and cytochrome c oxidase are present at all stages of gametogenesis as well as in the somatic cells of the testis and in the somatic cells of epididymis. Substantial amounts of copper can also be found in liquids associated with sperm in the epididymis and prostate. Copper also affects the integral androgen distribution in terms of fertility on the line hypothalamic-pituitary-testis. Both copper increase and deficiency leads to a significant reduction in male fertility, which spans the entire spectrum of abnormalities at the sperm level, male gonad, production of hormones and distribution of micronutrients such as zinc and iron. Nowadays, the effects of copper on gametes production have become more important and are connected with the increasing levels of pollution with heavy metals in environment.
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PMID:Role of copper in the process of spermatogenesis. 2879 60

Progressive functional maturation of spermatozoa is completed during the transit of these cells through the epididymis, a tubule structure connecting a testicle to a vas deferens. Epididymal epithelial cells by means of their secretory and absorptive functions determine a highly specialized luminal microenvironment containing multiple organic and inorganic components. The latter include copper ions, which due to their redox properties are indispensable for critical homeostatic processes occurring in spermatozoa floating in different part of epididymis but can be potentially toxic. Main purpose of our study was to determine epididymal region-dependent expression and localization of copper transporters ensuring a tight control of copper concentration in epididymal fluid. We also aimed at identifying proteins responsible for copper uptake by spermatozoa and verifying whether this process is coordinated with copper supply to superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Our study identifies two ATPases-ATP7A, ATP7B and Slc31a1, major copper importers/exporters depending on their differential expression on epididymal polarized epithelial cells of the caput, corpus, and cauda. Next, ceruloplasmin seems to be a chief protein transporting copper in the epididymal fluid and providing this biometal to spermatozoa. The entry of copper to germ cells is mediated by Slc31a1 and is correlated with both expressions of copper chaperone for superoxide dismutase (CCS), copper chaperone directly providing copper ions to SOD1 and with the expression and activity of the latter. Our results outline a network of cooperating copper binding proteins expressed in epididymal epithelium and in spermatozoa that orchestrate bioavailability of this microelement for gametes and protect them against copper toxicity.
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PMID:Molecular machinery providing copper bioavailability for spermatozoa along the epididymial tubule in mouse. 3099 85