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Results for “Bioactive peptide”

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At least 1,099 records · Page 61Linked to original sources

PubMed1993

Plasma endopeptidase 24.11 (enkephalinase) activity is markedly increased in cholestatic liver disease.

Endopeptidase 24.11 (enkephalinase), an enzyme known to be present in plasma and liver, is capable of metabolizing a substantial number of bioactive peptides. We measured plasma endopeptidase 24.11 activity in normal subjects and in patients with chronic hepatocellular disease or chronic cholestatic liver disease. The mean level of plasma endopeptidase 24.11 activity was 13 times higher in cholestatic patients than in controls or patients with hepatocellular disease (p < 0.01). Plasma endopeptidase 24.11 activity in patients correlated closely with traditional serum markers of cholestasis, including levels of alkaline phosphatase, gamma-glutamyltranspeptidase and aminopeptidase (p < 0.01 for all). However, plasma endopeptidase 24.11 activity correlated poorly with serum ALT aminotransferase level (p = NS), indicating that it is not a marker of hepatocellular disease. The lack of overlap between plasma endopeptidase 24.11 activity in cholestatic patients and noncholestatic liver disease controls suggests that this enzyme activity is a useful biochemical marker of cholestasis. In addition, because of the broad spectrum of peptides metabolized by endopeptidase 24.11, increased plasma endopeptidase 24.11 activity may contribute to the pathophysiology of the syndrome of cholestasis.

Adult↗

PubMed1994

Regulation of carboxypeptidase E. Effect of Ca2+ on enzyme activity and stability.

Carboxypeptidase E (CPE), an enzyme that functions in the post-translational processing of bioactive peptides, is a member of the metallocarboxypeptidase gene family. A 12-residue region of CPE has 70% amino acid identity with the bacterial enzyme carboxypeptidase T (CPT); in CPT, this region has been identified previously as the Ca(2+)-binding region (Teplyakov, A., Polyakov, K., Obmolova, G., Strokopytov, B., Kuranova, I., Osterman, A., Grishin, N., Smulevitch, S., Zagnitko, O., Galperina, O., Matz, M., and Stepanov, V. (1992) Eur. J. Biochem. 208, 281-288). Using 45Ca2+ binding, we determined that CPE binds Ca2+. To investigate the potential function for the interaction of CPE with Ca2+, we investigated the effect of Ca2+ on aggregation, thermostability, and enzyme activity of CPE. CPE does not aggregate under a variety of Ca2+ concentrations at either pH 5.5 or 7.5, and with protein concentrations ranging from 10 to 100 micrograms/ml. Whereas Ca2+ generally stabilizes proteins to thermal denaturation, CPE was destabilized by Ca2+ and stabilized by low concentrations of EGTA. The Ca(2+)-induced destabilization of CPE was more pronounced at pH 8 than at lower pH values. At pH 8, CPE was unstable even at 37 degrees C, with approximately 40% loss of activity upon incubation for 30 min in the absence of added Ca2+ and 70% loss of activity upon incubation in the presence of 10 mM CaCl2. Enzyme activity was not influenced by added Ca2+, but was stimulated by micromolar concentrations of EGTA; kinetic analysis showed this stimulation to be due to a change in Vmax, and not Km. Taken together, these data suggest that Ca2+ plays a role in the regulation of CPE activity.

Amino Acid Sequence↗

PubMed1993

Hepatobiliary handling of iodine-125-Tyr3-octreotide and indium-111-DTPA-D-Phe1-octreotide by isolated perfused rat liver.

Radiolabeled bioactive peptides may show receptor-mediated binding to tumors, making them suitable for scintigraphic imaging. The liver is an important organ for peptide clearance. To gain insight into the uptake and intracellular processing of somatostatin analogs, we compared the hepatobiliary handling of 125I-Tyr3-octreotide and 111In-DTPA-D-Phe1-octreotide, which are successfully used to image somatostatin receptor-positive tumors in vivo in isolated recirculating perfused rat livers. Sixty minutes following administration of the radiolabeled peptides, perfusion medium and biliary radioactivity were analyzed. Radioiodinated Tyr3-octreotide was rapidly cleared by the liver and 60% of the dose was excreted intact into the bile after 60 min. In contrast, 111In-DTPA-D-Phe1-octreotide was not cleared by the liver; medium radioactivity levels remained about constant and only 2% of the dose was found in the bile. These results are in agreement with in vivo findings in rats and humans. We concluded that isolated rat liver perfusion is a good system to rapidly gain insight into the hepatic handling of radiopharmaceuticals.

Animals↗

PubMed1993

Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis.

Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non-neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing.

Animals↗

PubMedDate not supplied

A role of transforming growth factor-beta 1 in the control of corneal neovascularization.

Transforming growth factor beta 1 (TGF-beta 1) has been implicated in both the stimulation of angiogenesis in vivo and in the inhibition of endothelial cell proliferation in vitro systems. In this study we present evidence showing that under certain experimental conditions TGF-beta 1 may inhibit neovascularization in vivo. TGF-beta 1 was incorporated into ethylene vinyl acetate copolymer (Elvax 40) matrixes which provide a valuable vehicle for the controlled and sustained delivery of bioactive peptides. The biological effectiveness of TGF-beta 1 sequestered in polymer matrices was assessed by measuring the inhibition of [3H]-thymidine incorporation into the DNA of cultured mink lung epithelial cells. Neovascularization was induced in both corneas of albino rabbits by one deep-seated limbal silk suture. Elvax 40 matrixes loaded with TGF-beta 1 (release rate, 1.66 ng/24 h) were implanted in rabbit corneal stroma. "Empty" polymers in the contralateral eye served as controls. Aliquots of aqueous fluid were withdrawn, and the presence activity of phagocytic cells was assessed by the production of superoxide anion (O2) which was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C. Polymer-enclosed TGF-beta 1 implanted in rabbit corneas significantly suppressed angiogenesis (2.65 +/- 0.4 mm compared to 3.05 +/- 0.3 mm in contralateral controls p < 0.05). Superoxide production in 100 microliters aliquots of aqueous fluid was 0.95 +/- 0.18 and 0.6 +/- 0.18 nmol O2/10 min in control eyes and in the eyes bearing sequestered TGF-beta 1, respectively (p < 0.02). These results indicate that under the experimental conditions selected in this study, TGF-beta 1 significantly suppressed in vivo angiogenesis.

Animals↗

PubMedDate not supplied

Production of radiolabeled neuropeptide precursors by in vitro transcription and translation.

Bioactive peptide hormones and neurotransmitters are required for neuroendocrine regulation of cellular functions. Importantly, proteolytic processing of inactive neuropeptide precursors is required to generate physiologically active peptide hormones and neurotransmitters. Studies of the processing enzymes require authentic neuropeptide precursors as substrates, rather than peptide substrates. This study demonstrates an efficient method to general 35S-precursors from cloned cDNAs by in vitro transcription and translation. In vitro transcription of neuropeptide cDNAs with SP6 RNA polymerase generates large amounts (micrograms) of corresponding RNAs. Subsequent in vitro translation of RNAs with wheat germ extract and 35S-methionine generates large quantities of 35S-precursors (10-25 million cpm 35S-precursor protein per reaction) with high specific radioactivity. The radiolabeled precursor substrates offer a reliable, sensitive and accurate method for detecting the proteolytic activity. Importantly, specific detection of the primary proenkephalin processing activity in chromaffin granules by 35S-enkephalin precursor as substrate, but not by peptide methylcoumarinamide (MCA) substrates, illustrates the significance of using full-length precursor to detect appropriate processing enzymes. This study demonstrates that efficient production of radiolabeled neuropeptide precursors by in vitro transcription and translation will be useful for in vitro assays of relevant processing proteases.

Animals↗

PubMed1996

Immunoglobulins and complement deposits in mitroflow pericardial bioprosthetic heart valves--a contributing factor to structural deterioration.

BACKGROUND AND AIMS OF THE STUDY: Twenty-two bovine pericardial Mitroflow prostheses were explanted after 73-114 months from either the aortic or mitral position because of clinical failure. All the samples exhibited cuspal tears and foldings. Eleven prostheses were calcified. The aim was to study biological factors involved in the structural deterioration. METHODS: Histologic and biochemical assays were carried out on the deteriorated, non-calcified and on the calcified leaflets. Labelled antibodies and avidinbiotinyilated peroxydase complex were used to detect plasma proteins and cells in the cusps. RESULTS: Fibrin covered the cuspal surface and accumulated in the deep disrupted layers (19/22). Scattered fibronectin filaments were seen across the transversal sections (20/22). IgG, complement fractions C1q, C3, C4 (20/22), macrophages (sixteen) and cells containing granulocyte elastase were revealed in the altered matrix. These plasma proteins and cells were detected in the disintegrated matrix of non-calcified and of calcified leaflets. IgA was present in amorphous cuspal thickenings with lipid infiltration (12/22). Western blot analysis of the PBS-2% SDS extracts from the leaflets indicated the breakdown of fibrinogen/fibrin, fibronectin and of complement proteins C3, C4 and C5. CONCLUSIONS: The results suggest the activation of the complement by the non-hemocompatible, chemically processed bovine pericardium. The bioactive peptides generated in this process can stimulate monocyte migration, phagocytosis and exocytosis of proteases able to degrade the glutaraldehyde cross-linked macromolecular matrix. These biological factors can contribute, together with the mechanical stress, to the structural deterioration of the bioprosthesis.

Aged↗

PubMed1998

Lipopolysaccharide a virulence factor of Helicobacter pylori: effect of antiulcer agents.

Helicobacter pylori plays a major role in the pathogenesis of gastric disease. The gastric epithelial integrity is compromised by the H. pylori cell wall lipopolysaccharide untoward effect on the gastric epithelial cell receptors interaction with proteins of extracellular matrix, glycoproteins of mucus coat, and bioactive peptides. These interactions cause the weakening of the mucus coat rendering the underying epithelium vulnerable to noxious luminal contents and disrupting the regulatory feedback of somatostatin and gastrin. Moreover, H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and these changes are reflected in the increased epithelial cell apoptosis. These findings thus identify cell wall lipopolysaccharide as a virulent factor responsible for the H. pylori effect on gastric epithelium. The effect of antiulcer agents on the interference of lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding. In the case of somatostatin-receptor binding, sulglycotide followed by sucralfate and ebrotidine showed the most potency in of reversing the effect of H. pylori lipopolysaccharide. Thus these antiulcer agents have a great promise in the treatment gastric diseases associated with H. pylori infection.

Anti-Ulcer Agents↗

PubMed1998

Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma.

PURPOSE: A number of peptidases which can metabolize certain bioactive peptides and growth factors have been identified in seminal plasma. Our goal in this study was to determine molecular properties and the tissue source(s) for one of these peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma. MATERIALS AND METHODS: We measured the activities of DPP IV with the dipeptide glycylprolyl-p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of men who were vasectomized or with different sperm concentrations, and in prostatic and seminal vesicle secretions of men undergoing prostatic surgery. RESULTS: DPP IV in seminal plasma of vasectomized men was a membrane associated dimer comprised of subunits of approximately 110 kDa. Its activity did not differ in seminal plasmas of vasectomized, azoospermic, oligozoospermic and normozoospermic men indicating no correlation with the concentration of sperm originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity were present in prostatic secretion, but absent from that of the seminal vesicles. These data indicate that the prostate gland is the primary source of DPP IV activity in seminal plasma. There was little variation in its activities in repeat seminal plasma samples from the same individual, and there was no change in its activity with age to 50 years. CONCLUSIONS: DPP IV in seminal plasma was derived from the prostate gland and it may be useful as a bioindicator of prostate function and/or disease with age in men.

Dipeptidyl Peptidase 4↗

PubMed2003

Bioactivity of a peptide derived from acetylcholinesterase: electrophysiological characterization in guinea-pig hippocampus.

Acetylcholinesterase is well known to have noncholinergic functions. Only recently, however, has the salient part been identified of the molecule responsible for these nonclassical actions, a peptide of 14 amino acids towards the C-terminus of acetylcholinesterase. The aim of this study was to test the bioactivity of this 'acetylcholinesterase-peptide' using intracellular recordings in guinea-pig hippocampal slices. In the presence of tetrodotoxin, acetylcholinesterase-peptide alone affected neither the membrane potential nor the input resistance of CA1 neurons; however, a modulatory action was observed, as a concentration-dependent decrease of N-methyl-d-aspartic acid-induced depolarization. When calcium potentials were elicited by a depolarizing current pulse, application of acetylcholinesterase-peptide increased or reduced the degree of calcium spike firing in, respectively, the presence or absence of the N-methyl-d-aspartic acid antagonist d(-)-2-amino-5-phosphonopentanoic acid. In contrast, a peptide derived from the equivalent region of butyrylcholinesterase, which also hydrolyses acetylcholine, had no effect. In conclusion, acetylcholinesterase-peptide has a selective bioactivity in the hippocampus; it could thus offer new ways of targeting mechanisms of calcium-induced neurotoxicity.

Acetylcholinesterase↗

PubMed2006

Identification of a peptide mimic of bioactive gibberellins with affinity to GA 2-oxidase.

Previously we reported the first example of peptide mimics of a small hydrophobic molecule, a phytohormone gibberellin. The second peptide mimic of gibberellin has been identified from random peptide libraries by its affinity to a type of catalyzing enzyme of gibberellins, which specifically recognizes bioactive gibberellins. These results suggest that even hydrophobic compounds can be mimicked by peptides.

Catalysis↗

PubMed1991

R15 alpha 1 and R 15 alpha 2 peptides from Aplysia: comparison of bioactivity, distribution, and function of two peptides generated by alternative splicing.

The mRNA precursor encoded by the R15 gene is alternatively spliced in different neurons to form two related variants, R15-1 and R15-2 mRNA. One of the peptides encoded by the R15-2 mRNA, the R15 alpha 1 peptide, is expressed in the endogenously bursting neuron R15 and mediates some of its central and peripheral synaptic actions. In this study we found that the R15 alpha 2 peptide, which is encoded by the R15-1 mRNA, is synthesized in other neurons in the abdominal ganglion and is also bioactive. The R15 alpha 1 and R15 alpha 2 peptides were found to exert many similar actions on the cardiovascular, digestive, respiratory, and reproductive systems. However, the differences between many of the pharmacological effects of the R15 alpha 1 and R15 alpha 2 peptides indicate that alternative splicing in this system results in two functionally different peptides. Widespread immunoreactivity was found for an antibody directed against the R15 alpha 2 peptide, both in the central nervous system and the periphery. But because of the shared sequence with the R15 alpha 1 peptide, the antibody cross-reacts with the R15 alpha 1 peptide. To distinguish immunocytochemically between the two peptides, we also raised a second antibody that recognizes only the R15 alpha 1 peptide. This antibody labeled the cell body of only one neuron in the central nervous system, R15, although widespread immunoreactivity was found in axons and varicosities in the periphery.

Animals↗

PubMed2006

[Research development of chemistry and bioactive activity of plant peptides].

As the technologies of separation, purification and determination develop rapidly, more and more peptide compounds, which have special bioactive and medical value, have been separated from natural plants, such as oligopeptides and cyclopeptides. The chemical structures and function of these plant peptides have been researched profoundly. This paper mainly reviews the composition, structure, bioactive function and medicine value of representative plant peptides in recent years, and can give some references about research and application of plant bioactive peptides.

Animals↗

PubMed2002

Glyproline peptide family: review on bioactivity and possible origins.

Glyproline peptide family includes the simplest proline-containing linear peptides PG, GP, PGP, respective peptides with hydroxylated proline residues and (with some restriction) cyclic PG. Having close structural resemblance they display many similar bioactivities. The suppression of some reactions of blood coagulation and platelet aggregation and protection of gastric mucosa against various ulcerogenic factors are the most important glyproline effects. Glyprolines have two common putative sources: (1) collagen and elastin synthesis and catabolism, and (2) penetration of proline-containing di- and tripeptides from food protein hydrolysate from the intestine into bloodstream. Possible physiological and biochemical mechanisms of glyproline bioactivities are under discussion.

Journal Article↗

PubMed1999

Rolling Loop Scan: An Approach Featuring Ring-Closing Metathesis for Generating Libraries of Peptides with Molecular Shapes Mimicking Bioactive Conformations or Local Folding of Peptides and Proteins.

Libraries of loop-containing peptides (such as the one shown schematically) can be prepared from bis-N-alkylated peptides by ring-closing metathesis. In a general solid-phase procedure the peptides are accessible by site-specific N-alkylation. Since the amino acid side chains are not involved in cyclization, they remain available for interaction with, for example, a receptor.

Journal Article↗

PubMed2006

Regulation of G proteins by human 5-HT1a receptor TM3/i2 and TM5/i3 loop peptides.

A bioactive synthetic 11 amino acid peptide probe (P11) was constructed according to the published sequence of the human 5HT1a receptor. The probe was used to enhance understanding of cytoplasmic loop 2/G protein coupling and activation. Additionally, two peptides (P8, P9) from the cytoplasmic loop 3 region were synthesized and studied. These probes were tested in a model system of human 5HT1a receptor stably expressed in Chinese Hamster Ovary cells. In agonist inhibition studies, P11 was active in all three receptor preparations tested: whole cells, membrane bound, and solubilized. In analyses of the membrane bound receptor system, P11 demonstrated uncompetitive inhibition characteristics. When forskolin-stimulated cAMP levels were measured, P11 was inactive in this negatively coupled system. Utilizing a [35S]gamma-S-GTP incorporation assay, P11 was unable to stimulate G protein incorporation of GTP. While P8 and P9 were also broadly active as non-competitive agonist inhibitors, their characteristics differed in the signal transduction system. P8 and P9 did not significantly change forskolin-stimulated cAMP levels. However, P8 increased [35S]gamma-S-GTP incorporation, while P9 decreased incorporation. Thus, P11, a synthetic peptide from the TM3/i2 region of the receptor, provides suggestive evidence that this receptor region is involved in G protein coupling but not activation. On the other hand, P8 and P9 activities suggest that the TM5/i3 region is involved in both coupling to and regulation of G protein activity. The current evidence from these cytoplasmic loop regions is discussed in the overall context of an emerging model for human 5HT1a receptor-G protein interactions.

Amino Acid Sequence↗

PubMed2004

Recent advances in the investigation of the bioactive conformation of peptides active at the micro-opioid receptor. conformational analysis of endomorphins.

Despite of the recent advances in the structural investigation of complex molecules, the comprehension of the 3D features responsible for the interaction between opioid peptides and micro-opioid receptors still remains an elusive task. This has to be attributed to the intrinsic nature of opioid peptides, which can assume a number of different conformations of similar energy, and to the flexibility of the receptorial cavity, which can modify its inner shape to host different ligands. Due to this inherent mobility of the ligand-receptor system, massive efforts devoted to the definition of a rigid bioactive conformation to be used as a template for the design of new pharmacologically active compounds might be overstressed. The future goal might be the design of peptide or nonpeptide ligands capable of maximizing specific hydrophobic interactions. This review covers the recent opinions emerged on the nature of the ligand-receptor interaction, and the development of suitable models for the determination of the bioactive conformation of peptide ligands active towards micro-opioid receptors.

Binding Sites↗

PubMed1997

Biochemical properties of regulatory peptides derived from milk proteins.

Biologically active peptides derived from milk proteins are inactive within the sequence of the precursor proteins but can be released by enzymatic proteolysis. Based on structure-activity studies, peptides with a defined bioactivity show common structural features. Moreover, many milk protein-derived peptides reveal multifunctional bioactivities. Bioactive peptide fragments originating from milk proteins should be taken into account as potential modulators of various regulatory processes in the body. Opioid peptides are opioid receptor ligands with agonistic or antagonistic activities. Angiotensin converting enzyme (ACE) inhibitory peptides can exert an antihypertensive effect. Immunomodulating casein peptides have been found to stimulate the proliferation of human lymphocytes and the phagocytic activities of macrophages. Antimicrobial peptides have been shown to kill sensitive microorganisms. Antithrombotic peptides inhibit the fibrinogen binding to a specific receptor region on the platelet surface and also inhibit aggregation of platelets. Casein phosphopeptides can form soluble organophosphate salts and may function as carriers for different minerals, especially calcium. In relation to their mode of action, bioactive peptides may reach target sites (e.g., receptors, enzymes) at the luminal side of the intestinal tract or after absorption, in peripheral organs. The physiological significance of bioactive peptides as exogenous regulatory substances is not yet fully understood. Nevertheless, several bioactive peptides derived from milk proteins have been shown to exert beneficial physiological effects. Milk-derived peptides were already produced on an industrial scale and as a consequence these peptides have been considered for application both as dietary supplements in "functional foods" and as drugs.

Adjuvants, Immunologic↗