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 kinase Mirk/dyrk1B mediated the clonogenic growth of pancreatic cancer cells in earlier studies. It is now shown that Mirk levels increased 7-fold in SU86.86 pancreatic cancer cells when over a third of the cells were accumulated in a quiescent G(0) state, defined by Hoechst/Pyronin Y staining. Depletion of Mirk by a doxycycline-inducible short hairpin RNA increased the G(0) fraction to approximately 50%, suggesting that Mirk provided some function in G(0). Mirk reduced the levels of reactive oxygen species (ROS) in quiescent cultures of SU86.86 cells and of Panc1 cells by increasing transcription of the antioxidant genes ferroxidase, superoxide dismutase (SOD)2, and SOD3. These genes were functional antioxidant genes in pancreatic cancer cells because ectopic expression of SOD2 and ferroxidase in Mirk-depleted cells lowered ROS levels. Quiescent pancreatic cancer cells quickly lost viability when depleted of Mirk because of elevated ROS levels, exhibiting up to 4-fold less colony-forming activity and 4-fold less capability for dye exclusion. As a result, reduction of ROS by N-acetyl cysteine led to more viable cells. Mirk also destabilizated cyclin D1 and D3 in quiescent cells. Thus, quiescent pancreatic cancer cells depleted of Mirk became less viable because they were damaged by ROS, and had increased levels of G(1) cyclins to prime cells to escape quiescence.
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PMID:Mirk/Dyrk1B maintains the viability of quiescent pancreatic cancer cells by reducing levels of reactive oxygen species. 1935 55

A conventional approach in dairy cow nutrition programs during late gestation is to feed moderate-energy diets. The effects of the maternal plane of nutrition on immune function and metabolism in newborn calves are largely unknown. Holstein cows (n=20) were fed a controlled-energy (CON) diet (1.24 Mcal/kg) for the entire dry period (~50 d) or the CON diet during the first 29 d of the dry period followed by a moderate-energy (OVE) diet (1.47 Mcal/kg) during the last 21 d prepartum. All calves were weighed at birth before first colostrum intake. Calves chosen for this study (n=6 per maternal diet) had blood samples harvested before colostrum feeding (d 0) and at 2 and 7 d of age. Blood samples were used to determine metabolites, acute-phase proteins, oxidative stress markers, hormones, phagocytic capacity of polymorphonuclear leukocytes (PMN) and monocytes, and total RNA was isolated from PMN. Calves from OVE dams weighed, on average, 5kg less at birth (44.0 vs. 48.6kg) than calves from CON dams. Blood glucose concentration in OVE calves had a more pronounced increase between 0 and 2 d than CON, at which point phagocytosis by PMN averaged 85% in OVE and 62% in CON. Compared with CON, calves from OVE had greater expression of TLR4, but lower expression of PPARA and PPARD at birth. Expression of PPARG and RXRA decreased between 0 and 2 d in both groups. Concentrations of leptin, cholesterol, ceruloplasmin, reactive oxygen metabolites, myeloperoxidase, retinol, tocopherol, IgG, and total protein, as well as expression of SOD2 and SELL increased markedly by 2 d in both groups; whereas, cortisol, albumin, acid-soluble protein, NEFA, insulin, as well as expression of IL6, TLR4, IL1R2, LTC4S, and ALOX5 decreased by 2 d. By 7 d of age, the concentration of haptoglobin was greater than precolostrum and was lower for OVE than CON calves. Our data provide evidence for a carry-over effect of maternal energy overfeeding during the last 3 wk before calving on some measurements of metabolism in the calf at birth and the phagocytic capacity of blood neutrophils after colostrum feeding. It might be feasible to design nutrient supplements to fortify colostrum in a way that metabolic and immunologic capabilities of the calf are improved.
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PMID:Effect of the level of maternal energy intake prepartum on immunometabolic markers, polymorphonuclear leukocyte function, and neutrophil gene network expression in neonatal Holstein heifer calves. 2358 95

The study was conducted to investigate the effects of dietary administrations of four nutraceuticals in dogs. Seventy four dogs were enrolled in the trials, 24 healthy dogs were fed with a control diet (CT) and the experimental groups received for 60days the same diet supplemented with nutraceuticals, namely Echinacea angustifolia (EA, 0.10mg/kg live weight as echinacoside; 14 dogs), Vaccinium myrtillus (VM, 0.20mg/kg live weight as anthocyanidin, 13 dogs), Curcuma longa (CL, 6.60mg/kg live weight as curcumin, 18 dogs with arthrosis), and Sylibum marianum (SM, 1.5mg/kg live weight as sylibin, 8 dogs with hepatopathy). Dogs were weighted at the beginning of study and blood samples were collected at the beginning (T0) and at the end (T60) of the study. VM significantly down regulated TNF, CXCL8, NFKB1 and PTGS2 and decreased plasma ceruloplasmin (CuCp). The activity of EA was evidenced by the significant decrease of TNF and NFKB1 expression and CuCp levels and by the increase of plasma Zn. Administration of CL caused a significant decrease of CuCp and increase of Zn and a down regulation of TNF, CXCL8, NFKB1 and PTGS2, corroborating the anti-inflammatory action of curcuminoids. After 60days of treatment with SM, plasma ALT/GPT activity was reduced and paraoxonase was increased, supporting the antioxidant activity of silymarin, also confirmed by the significant up regulation of SOD2. Results indicated that nutraceutical administrations in dogs can be an interesting approach to modulate immune response in order to improve health condition of animals.
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PMID:Nutrigenomic activity of plant derived compounds in health and disease: Results of a dietary intervention study in dog. 2789 63