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At least 199 records · Page 11Linked to original sources
PubMed1992

Induction by beta-estradiol of vitellogenin in striped bass (Morone saxatilis): characterization and quantification in plasma and mucus.

Striped bass (Morone saxatilis) were implanted with beta-estradiol to induce the production of vitellogenin, the egg yolk precursor produced by the liver. Electrophoretic analysis revealed that beta-estradiol caused marked production of a plasma protein of apparent molecular mass 170 kDa. Size exclusion chromatography suggested that the estradiol-induced protein circulated as a dimer. This protein was purified from the plasma of estradiol-treated fish by DEAE-agarose column chromatography and used to induce antibodies in rabbits and goats. Western blots revealed that the antiserum bound to the putative vitellogenin in plasma from estradiol-treated fish and adult females, but not with any proteins in male plasma. Western blot of ovarian extract revealed several smaller immunoreactive protein bands and supported the identity of the purified protein as vitellogenin. A competitive ELISA was developed with sensitivity in a range from 8 to 1000 ng/ml. Plasma concentrations of adult females during their spawning migration ranged from 100 to 600 micrograms/ml. Western blot of mucus extract revealed the presence of a 170-kDa protein in vitellogenic female fish along with several minor bands ranging from 50 to 110 kDa. Positive immunoreactivity was present in the surface mucus of all females and in none of the males collected during a spawning migration in the Hudson River.

Animals↗
PubMed2005

Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice.

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes.

Angiopoietin-Like Protein 4↗
PubMed2007

Overexpression of angiopoietin-like protein 4 alters mitochondria activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice.

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly produced from fat tissue and liver. Recent data from others and our laboratory have demonstrated this protein to be an important player in energy metabolism and insulin sensitivity. However, the molecular mechanisms underlying its metabolic actions remain elusive. In this study, we have employed a two-dimensional fluorescence difference gel electrophoresis technique to study the protein profiles in the livers of db/db mice treated with or without ANGPTL4. When compared with those of lean mice, 118 proteins were found to be up- or down-regulated in db/db mice. Adenovirus-mediated overexpression of ANGPTL4 could reverse a large portion of the up- or down-regulated proteins to control levels. Especially, a number of mitochondria proteins were down-regulated by ANGPTL4 to a great extent. Chronic treatment with ANGPTL4 resulted in an elevated activity of mitochondria respiratory chain complexes II-III and IV in db/db mice. Additionally, several key enzymes in the methionine/homocysteine metabolic cycle were found to be increased in db/db diabetic mice but decreased by ANGPTL4 treatment. HPLC analysis consistently revealed that ANGPTL4 could significantly restore the augmented S-adenosylmethionine levels and S-adenosylmethionine/S-adenosylhomocysteine ratios in livers of db/db mice. In summary, our results suggest that ANGPTL4 might elicit its metabolic effects through modulating the mitochondria functions and methionine metabolic cycles in the liver tissue.

Adenoviridae↗
PubMed1999

[Molecular signals in protein sorting in epithelial cells: implication of the transmembrane domain and the post-translational process].

Protein sorting in epithelial cells is the major event that drive the onset and the maintenance of the functional cell polarity. A lot of interdependent steps are involved in protein sorting and targeting. Recent data describing the last results obtained in this field will be reviewed in the first part of this article. Molecular signals harbored by proteins to specify their destination are thought to be the driven force to sort given protein in a given pathway. The basolateral targeting signals so far identified are known for several years and are of the same nature, whereas apical targeting signals are still discussed and are of diverse molecular nature. Dipeptidyl peptidase IV (DPP IV/CD26) targeting signals have not been described so far and it will be interesting to study these signals, since the protein reach the apical membrane of epithelial cells through different pathways that strongly depend on the cell type considered. These different pathways result in DPP IV membrane localizations that may explain the multifunctional properties of DPP IV such as enzymatic digestion, interaction with extracellular matrix proteins, capture and transport of circulating proteins. We have undertaken the study of DPP IV molecular targeting signals and we will described here how the transmembrane domain and the glycosylation of the ectodomain may be involved in DPP IV apical targeting, with a special reference to the cell type specificity.

Animals↗
PubMed1999

[Reestablishment of plasma proteins after plasmapheresis in patients with paraproteinemic hemoblastosis].

AIM: To study the effect of plasmapheresis (PA) on the changes in plasma total protein in the PA intervals in patients with paraproteinemic hemoblastosis (PPH). MATERIALS AND METHODS: 26 PPH patients underwent 80 PA procedures to remove macromolecular pathological proteins and diminish blood viscosity. Before PA the patients were examined hematologically, biochemically. Total protein concentration in plasma was measured before and after PA, in the removed plasma. RESULTS: PA promoted total protein lowering in plasma to 65-85% of the baseline irrespectively of PA technique. After PA the proteins gradually rose. Contents of circulation proteins were found unrelated to the number of PA procedures and averaged 70% of the PA-removed protein. CONCLUSION: The trends in recovery of plasma proteins after PA help to explain therapeutic effect in combination of PA with chemotherapy of paraproteinemic hemoblastoses.

Blood Proteins↗
PubMed2003

Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin.

Adiponectin or adipocyte complement-related protein of 30 kDa (Acrp30) is a circulating protein produced exclusively in adipocytes. Circulating Acrp30 levels have been associated with insulin sensitivity in adult mice and humans, yet the Acrp30 profile over the lifespan and its hormonal regulation in vivo have not been previously described. Hence, we set forth to determine whether hormonal and metabolic changes associated with sexual maturation, reproduction, aging, and calorie restriction affect Acrp30. In mice, Acrp30 levels increase during sexual maturation by 4-fold in males and 10-fold in females. Neonatal castration (CX) allows Acrp30 of adults to reach female levels. CX in adults does not lead to female Acrp30 levels unless glucocorticoid exposure is elevated simultaneously by implant. Ovariectomy of infant mice does not interfere with the pubertal rise of Acrp30. However, ovariectomy in adults increases Acrp30. Estrogen suppressed Acrp30 in mice and 3T3-L1 adipocytes. In parallel to changes in estrogen action, Acrp30 decreased in late gestation but increased in both calorie-restricted and old (anovulatory) mice. The reduction of Acrp30 in lactating dams is consistent with a suppressive effect of prolactin and a stimulating effect of bromocriptine. In summary, Acrp30 levels in serum are under complex hormonal control and may play a key role in determining systemic insulin sensitivity under the respective conditions.

Adipocytes↗
PubMed2001

The adipocyte-secreted protein Acrp30 enhances hepatic insulin action.

Acrp30 is a circulating protein synthesized in adipose tissue. A single injection in mice of purified recombinant Acrp30 leads to a 2-3-fold elevation in circulating Acrp30 levels, which triggers a transient decrease in basal glucose levels. Similar treatment in ob/ob, NOD (non-obese diabetic) or streptozotocin-treated mice transiently abolishes hyperglycemia. This effect on glucose is not associated with an increase in insulin levels. Moreover, in isolated hepatocytes, Acrp30 increases the ability of sub-physiological levels of insulin to suppress glucose production. We thus propose that Acrp30 is a potent insulin enhancer linking adipose tissue and whole-body glucose metabolism.

Adipocytes↗
PubMed1989

Is a decrease in plasma oncotic pressure enough to explain the edema of pregnancy?

The balance of fluid across capillaries is given by the Starling equation. Because the plasma protein concentration (one of its components) is decreased in pregnancy, we decided to explore the question as to whether hypoproteinemia with intact protein mass (produced by blood volume expansion) or hypoproteinemia with decreased total protein mass (produced by removal of circulating proteins) alters the oncotic pressure differences across capillaries. We calculated the oncotic pressure difference obtained in seven nonpregnant ewes during periods of normoproteinemia and hypoproteinemia; the influence of fluid infusion under both conditions was also observed. There was an increase in the oncotic pressure difference across the capillary wall during hypoproteinemia produced by a decrease in the total protein mass (p less than 0.01); however, the response to hypoproteinemia produced by fluid infusion was similar (p greater than 0.1). The venous pressure (used as an index of interstitial fluid pressure changes) did not differ in either hypoproteinemia or fluid infusion. Capillary permeability was decreased during hypoproteinemia, as evidenced by a higher lymph/protein ratio of labeled albumin during the control period (p less than 0.05). In conclusion, during a state of decreased plasma protein concentration similar to that of pregnancy, the difference in the oncotic pressure and hydrostatic pressure forces acting to prevent transfer of fluid to the interstitium is increased. Therefore other factors that influence fluid transfer across the capillaries must be investigated to explain the edema of pregnancy.

Animals↗
PubMed1976

Plasma volume changes after infusion of various plasma expanders.

In the immediate post-operative period after moderate surgical procedures, 1 litre of a colloid solution or saline was given intravenously. The plasma volume expansion after infusion of dextran 70 (Macrodex), hydroxyethylstarch (Volex), polygelatin (Haemaccel), albumin and saline was found to be between 790 and 180 ml. The most efficent plasma expander was dextran, followed by hydroxyethylstarch. Polygelatin and saline did not give full restitution, although twice the calculated loss was infused. Total plasma protein concentration was lowered in all groups in proportion to the dilution, except for the patients given albumin, in whom the concentration of total protein increased. Calculation of the total circulating protein mass showed no decrease during the period immediately after the infusion. This investigation has demonstrated that the most efficient plasma volume expander is dextran but that hydroxyethylstarch offers an almost equal alternative in terms of volume expansion. Dextran, however, exerts an advantageous effect on the microcirculation. As the metabolic pathways of hydroxyethylstarch have not yet been further explored, dextran is preferred when using artificial colloids. Judged by its secondary effects alone, including the influence on plasma protein patterns, albumin seems to be the compound of choice. Polygelatin and saline are not efficient expanders when hypovolaemia is to be corrected rapidly.

Adult↗
PubMed2002

Interferon-alpha induces interleukin-18 binding protein in chronic hepatitis C patients.

Interleukin-18 (IL-18), derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. IL-18 binding protein (IL-18BP) is a circulating protein that binds IL-18 and neutralizes its activity. Since IL-18 production is increased in chronic HCV infection, we asked whether IFN-alpha might act on the IL-18/IL-18BP system in HCV patients. IL-18BP, total and free IL-18 plasma levels were determined in 13 HCV patients receiving 1 x 107 IU IFN-alpha subcutaneously daily for 28 days. The in vitro effects of IFN-alpha on macrophage IL-18BP and IL-18 were studied by enzyme-linked immunosorbent assays and Northern analysis. IFN-alpha administration increased IL-18BP plasma levels 3.24 fold 24 h after institution of therapy, resulting in a 67.4% reduction of free IL-18. Total IL-18 levels decreased from day +24 on. In vitro, IFN-alpha diminished IL-18 release from macrophages of healthy volunteers and chronic HCV patients. On top of its inhibitory effects on IL-1 and TNF-alpha release, IFN-alpha also exerts its anti-inflammatory action in vivo by induction of IL-18BP. These anti-inflammatory properties might account - together with its antiviral action - for its clinical efficacy in chronic hepatitis C.

Down-Regulation↗
PubMed2005

Mechanisms of vascular calcification in renal disease.

Vascular calcification is commonplace in patients with end-stage renal disease where it develops rapidly and predicts a variety of adverse outcomes. The processes responsible for vascular calcification have been the focus of much research, aided in recent decades by molecular genetic techniques and in vitro models. Converging evidence now suggests that vascular calcification is an active, regulated process, with abundant similarities to the process of skeletal mineralization. Using an in vitro model of calcifying vascular smooth muscle cells (VSMCs), we have shown that a mineral imbalance induces VSMC apoptosis, and that VSMC apoptotic bodies and vesicles can nucleate basic calcium phosphate in the form of hydroxyapatite, the same mineral found in bone. Gene expression studies suggest that the normal vessel wall expresses proteins such as matrix Gla protein that inhibit calcification. In addition, circulating proteins such as fetuin-A are produced at remote sites and act to inhibit soft tissue calcification systemically. However, down-regulation or perturbation of these proteins may lead to a phenotypic transformation of VSMCs to osteo/chondrocytic-like cells while the calcified environment may stimulate macrophages to adopt osteoclastic properties. Both clinical and basic research findings indicate an inverse relationship between bone mineralization and vascular calcification. The mechanisms linking these two processes are a topic for further investigation, with current theories proposing a role for lipids, common regulatory molecules, and calcium and bone turnover. We have synthesized these findings into a theoretical model offering a putative pathway for the development of severe vascular calcification in end-stage renal disease.

Animals↗
PubMed2004

Plasma protein C levels in patients with acute lung injury: prognostic significance.

Decreased circulating protein C is a marker of a prothrombotic state that has been associated with poor clinical outcomes in sepsis. However, protein C has not been measured in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). In this study, we measured circulating and intra-alveolar concentrations of protein C in 45 patients with ALI/ARDS from septic and nonseptic causes. Plasma protein C levels were lower in ALI/ARDS compared with normal controls. Lower levels of plasma protein C were associated with worse clinical outcomes, including death, fewer ventilator-free days, and more nonpulmonary organ failures, even when only patients without sepsis were analyzed. In summary, the protein C system is markedly disrupted in patients with ALI/ARDS from both septic and nonseptic causes. The protein C system may be a therapeutic target in patients with ALI/ARDS.

Adult↗
PubMed2000

Expression of matrix metalloproteinase-2 and -9 and their inhibitors in peripheral blood cells of patients with chronic hepatitis C.

BACKGROUND: To clarify whether circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) can be used as serum markers of fibroproliferation in chronic liver diseases, we studied the expression of MMP-2 and MMP-9 in relation to TIMP-1 and TIMP-2 in peripheral blood mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs), and compared this expression to circulating concentrations and hepatic histology in patients with chronic active hepatitis C (CAH). METHODS: Quantitative reverse transcription-PCR/ELISA assays were performed for MMP and TIMP RNA, and corresponding circulating protein concentrations were studied by ELISA in 20 healthy controls, 40 patients with CAH, and 20 patients with hepatitis C-induced cirrhosis (Ci). RESULTS: MMP-2 mRNA was found almost exclusively in the liver, MMP-9 mRNA in leukocytes. TIMP RNA-equivalents were decreased in MNLs of CAH patients, but neither MMP-9 nor TIMP RNA expression showed any correlation to the extent of inflammation and fibrosis. MMP-2 and TIMP-1 protein concentrations were increased in Ci patients and showed a wide overlap in CAH patients and healthy controls. MMP-9 values were lower in CAH and Ci patients than in healthy controls. TIMP-2 values showed a wide overlap in all three groups. The MMP-2/TIMP-1 and MMP-9/TIMP-1 ratios were lower in Ci patients than in healthy controls; the MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios were not different. Circulating TIMP-1 and the MMP-2/TIMP-1 ratio correlated to the inflammatory activity in liver biopsies, but only the circulating MMP-2/TIMP-1 ratio also correlated with the degree of fibrosis. CONCLUSIONS: Peripheral blood cell expression of MMP-2, MMP-9, and TIMP revealed no correlation with the circulating concentrations of these proteins. Only the circulating MMP-2/TIMP-1 ratio correlated to the histological degree of fibrosis in hepatitis C and should be further evaluated as a progression marker in patients with chronic liver disease.

Hepatitis C, Chronic↗
PubMed2003

Oligomerization and regulated proteolytic processing of angiopoietin-like protein 4.

Angiopoietin-like protein 4 (Angptl4) is a recently identified circulating protein expressed primarily in adipose tissue and liver. Also known as peroxisome proliferator-activated receptor (PPAR)-gamma angiopoietin-related, fasting induced adipose factor, and hepatic fibrinogen/angiopoietin-related protein, recombinant Angptl4 causes increase of plasma very low density lipoprotein levels by inhibition of lipoprotein lipase activity. Similar to angiopoietins and other angiopoietin-like proteins, Angptl4 contains an amino-terminal coiled-coil domain and a carboxyl-terminal fibrinogen-like domain. We report here that Angptl4 is evolutionarily conserved among several mammalian species and that full-length Angptl4 protein is an oligomer containing intermolecular disulfide bonds. Oligomerized Angptl4 undergoes proteolytic processing to release its carboxyl fibrinogen-like domain, which circulates as a monomer. Angptl4's N-terminal coiled-coil domain mediates its oligomerization, which by itself is sufficient to form higher order oligomeric structure. Adenovirus-mediated overexpression of Angptl4 in 293 cells shows that conversion of full-length, oligomerized Angptl4 is mediated by a cell-associated protease activity induced by serum. These findings demonstrate a novel property of angiopoietin-like proteins and suggest that oligomerization and proteolytic processing of Angptl4 may regulate its biological activities in vivo.

Amino Acid Sequence↗
PubMed1978

Circulating lymphocytes and the spread of myeloma. Review of the evidence.

Patients with myeloma harbour circulating lymphocytes which bear the idiotypic determinants (SIg-id+ cells) of their own myeloma protein. Circulating white cells with abnormal karyotypes have been found in other patients with this disease. SIg-id+ lymphocytes have also been identified in the peripheral blood of myeloma-tumour-bearing mice. Murine myelomas have been propagated in vivo from circulating mononuclear cells that possessed myeloma-tumour-associated antigens. This and other evidence reviewed here points strongly to the involvement of circulating lymphocyte-like stem cells in the spread of human myeloma.

Animals↗
PubMed1996

Evidence for the systemic delivery of a transgene product from salivary glands.

The aim of this study was to assess the feasibility of using gene transfer to salivary glands to direct the systemic delivery of therapeutic proteins in vivo. We used a replication-deficient recombinant adenovirus vector (Ad alpha 1AT) that encodes human alpha 1-antitrypsin (h alpha 1-AT), which we used as a marker protein. Ad alpha 1AT (5 x 10(9) pfu) was administered by retrograde ductal instillation to the submandibular glands of male rats. The amount of h alpha 1-AT found in the salivary glands, saliva, serum, and other tissues was analyzed by a sensitive enzyme-linked immunosorbent assay (ELISA). Maximal levels of the marker protein were detected at 24-48 hr post-virus administration for glands (274 ng/mg protein), saliva (approximately 313 ng/ml), and serum (approximately 5 ng/ml). Serum levels remained elevated for 96 hr, whereas the measured half-life for the marker protein was approximately 2 hr. Generally little to no h alpha 1-AT was detectable in most other organs. However, we were able to measure low levels of marker protein in tissues immediately surrounding infected glands. In all animals studied, levels of h alpha 1-AT were higher in the glandular venous effluent than in arterial blood. Similar results were found with parotid glands. The aggregate data demonstrate that salivary glands may be a target for the nonsurgical, systemic delivery of transgene-encoded therapeutic proteins for diseases that require relatively low circulating protein levels.

Adenoviruses, Human↗
PubMed1998

Measurement of dermal collagen synthesis rate in vivo in humans.

Accumulation of collagen produces organ dysfunction in many pathological conditions. We measured the fractional synthesis rate (FSR) of dermal collagen in five human volunteers from the increment of [13C]proline in detergent-soluble dermal collagen hydroxylated to hydroxyproline during a continuous infusion of L-[1-13C]proline. In these and eight other volunteers, we measured [13C]proline enrichment in skin aminoacyl-tRNA, skin tissue fluid amino acid, and plasma. The prolyl-[13C]tRNA enrichment was one-half that in tissue fluid proline and more than threefold less than in plasma. The FSR of dermal collagen was 0.076 +/- 0.063%/h (mean +/- SD), similar to previously reported rates for skeletal muscle contractile proteins and substantially slower than hepatically derived circulating proteins such as albumin or fibrinogen. We conclude that the FSR of human dermal collagen resembles that of other human proteins considered to display slow turnover. The current method for its measurement may be used to determine the regulation of collagen synthesis in other organs and disease states.

Collagen↗
PubMed1981

Elevated serum levels of the eosinophil granule major basic protein in patients with eosinophilia.

A radioimmunoassay was established for the human eosinophil granule major basic protein (MBP). The mean level of MBP in sera from 105 normal control patients was 454 ng/ml, whereas in a sample of 188 patients with various forms of diseases, including the hypereosinophilic syndrome, levels as high as 14,000 ng/ml were measured. Serum levels of MBP did not correlate with eosinophil counts in normal subjects, but a positive correlation was seen in patients with eosinophilia; the patients with eosinophil counts greater than 350/mm3 generally showed increased levels of MBP. Many patients with skin disease and normal eosinophil counts had elevated levels of serum MBP. Monomer MBP has a molecular weight of 9,300, but in sera of patients with eosinophilia, the MBP activity was of high molecular weight, greater than 50,000. Analyses of serum by Sephadex G-200 and by electrofocusing suggest that MBP is not simply polymerized, but rather is bound to a larger carrier molecule. Monomeric MBP can be isolated from serum by reduction of serum with dithiothreitol, alkylation with iodoacetamide, and acidification to pH 2 followed by fractionation on Sephadex G-50 at pH 2. Under these conditions, up to 80% of the MBP emerges in monomeric form. The results indicate that eosinophil granule proteins circulate in blood covalently bound to serum proteins, and that elevated concentrations of serum MBP are present in some diseases associated with eosinophilia.

Alkylation↗