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J. Michael Conlon - One of the best experts on this subject based on the ideXlab platform.
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Peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog Xenopus ruwenzoriensis (Pipidae)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2016Co-Authors: Laurent Coquet, Jolanta Kolodziejek, Norbert Nowotny, Thierry Jouenne, Jay D. King, J. Michael ConlonAbstract:Abstract The Uganda clawed frog Xenopus ruwenzoriensis with a karyotype of 2n = 108 is one of the very few vertebrates with dodecaploid status. Peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 6 peptides), Xenopsin precursor fragment (XPF; 3 peptides), caerulein precursor fragment (CPF; 8 peptides), and caerulein precursor fragment-related peptide (CPF-RP; 3 peptides). In addition, the secretions contained caerulein, identical to the peptide from Xenopus laevis , and two peptides that were identified as members of the trefoil factor family (TFF). The data indicate that silencing of the host-defense peptide genes following polyploidization has been appreciable and non-uniform. Consistent with data derived from comparison of nucleotide sequences of mitochrondrial and nuclear genes, cladistic analyses based upon the primary structures of the host-defense peptides provide support for an evolutionary scenario in which X. ruwenzoriensis arose from an allopolyploidization event involving an octoploid ancestor of the present-day frogs belonging to the Xenopus amieti species group and a tetraploid ancestor of Xenopus pygmaeus.
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Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).
Peptides, 2015Co-Authors: J. Michael Conlon, Milena Mechkarska, Jolanta Kolodziejek, Norbert Nowotny, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Jay D. KingAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), Xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation.
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Host-defense peptides from skin secretions of Fraser's clawed frog Xenopus fraseri (Pipidae): Further insight into the evolutionary history of the Xenopodinae.
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2014Co-Authors: J. Michael Conlon, Milena Mechkarska, Jolanta Kolodziejek, Norbert Nowotny, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert VaudryAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus fraseri Boulenger, 1905 (Pipidae) led to identification of 13 host-defense peptides. The primary structures of the peptides demonstrate that they belong to the magainin (3 peptides), peptide glycine–leucine-amide, PGLa (4 peptides), and Xenopsin-precursor fragment, XPF (2 peptides) families, first identified in Xenopus laevis , together with caerulein precursor fragment-related peptides, CPF-RP (4 peptides), first identified in Silurana tropicalis . In addition, the secretions contain a molecular variant of Xenopsin displaying the substitution Arg 4 → Lys compared with X. laevis Xenopsin and peptide glycine–tyrosine-amide (PGYa) (GRIIPIYPEFERVFA KKVYPLY.NH 2 ) whose function is unknown. The most potent antimicrobial peptide identified is CPF-RP-F1 (GFGSVLGKALKFGANLL.NH 2 ) with MIC = 12.5 μM against Staphylococcus aureus and 50 μM against Escherichia coli . On the basis of similarities in morphology and advertisement calls, X. fraseri has been placed in a species group that includes the octoploids Xenopus amieti and Xenopus andrei , and the tetraploid Xenopus pygmaeus. Cladistic analyses based upon the primary structures of magainin, PGLa, and CPF-RP peptides support a close evolutionary relationship between X. fraseri , X. amieti and X. andrei but suggest a more distant relationship with X. pygmaeus .
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Host-defense peptides from skin secretions of the octoploid frogs Xenopus vestitus and Xenopus wittei (Pipidae): insights into evolutionary relationships.
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2014Co-Authors: Milena Mechkarska, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Katarzyna Michalak, Pawel Michalak, J. Michael ConlonAbstract:Abstract The primary structures of host-defense peptides have proved useful in elucidating the evolution history of frogs. Peptidomic analysis was used to compare the diversity of host-defense peptides in norepinephrine-stimulated skin secretions from the octoploid frogs, Xenopus vestitus (Kivu clawed frog) and Xenopus wittei (De Witte's clawed frog) in the family Pipidae. Structural characterization demonstrated that the X. vestitus peptides belong to the magainin (3 peptides), peptide glycine–leucine–amide (PGLa; 4 peptides), Xenopsin-precursor fragment (XPF; 1 peptide), and caerulein-precursor fragment (CPF; 5 peptides) families. The X. wittei peptides comprise magainin (4 peptides), PGLa (1 peptide), XPF (2 peptides), and CPF (7 peptides). In addition, secretions from both species contain caerulein, identical to the peptide from Xenopus laevis , but X. wittei secretions contains the novel peptide [R4K]Xenopsin. The variability in the numbers of paralogs in each peptide family indicates a selective silencing of the host-defense peptide genes following the polyploidization events. The primary structures of the peptides provide insight into phylogenetic relationships among the octoploid Xenopus frogs. The data support a sister-group relationship between X. vestitus and Xenopus lenduensis , suggestive of bifurcating speciation after allopolyploidization, whereas X. wittei is more closely related to the Xenopus amieti – Xenopus andrei group suggesting a common tetraploid ancestor. Consistent with previous data, the CPF peptides showed the highest growth inhibitory activity against bacteria with CPF-W6 (GIGSLLAKAAKLAAGLV.NH 2 ) combining high antimicrobial potency against Staphylococcus aureus (MIC = 4 μM) with relatively low hemolytic activity (LC 50 = 190 μM).
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Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae
Pharmaceuticals, 2014Co-Authors: J. Michael Conlon, Milena MechkarskaAbstract:Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and Xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored.
Milena Mechkarska - One of the best experts on this subject based on the ideXlab platform.
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Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).
Peptides, 2015Co-Authors: J. Michael Conlon, Milena Mechkarska, Jolanta Kolodziejek, Norbert Nowotny, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Jay D. KingAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), Xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation.
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Host-defense peptides from skin secretions of Fraser's clawed frog Xenopus fraseri (Pipidae): Further insight into the evolutionary history of the Xenopodinae.
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2014Co-Authors: J. Michael Conlon, Milena Mechkarska, Jolanta Kolodziejek, Norbert Nowotny, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert VaudryAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus fraseri Boulenger, 1905 (Pipidae) led to identification of 13 host-defense peptides. The primary structures of the peptides demonstrate that they belong to the magainin (3 peptides), peptide glycine–leucine-amide, PGLa (4 peptides), and Xenopsin-precursor fragment, XPF (2 peptides) families, first identified in Xenopus laevis , together with caerulein precursor fragment-related peptides, CPF-RP (4 peptides), first identified in Silurana tropicalis . In addition, the secretions contain a molecular variant of Xenopsin displaying the substitution Arg 4 → Lys compared with X. laevis Xenopsin and peptide glycine–tyrosine-amide (PGYa) (GRIIPIYPEFERVFA KKVYPLY.NH 2 ) whose function is unknown. The most potent antimicrobial peptide identified is CPF-RP-F1 (GFGSVLGKALKFGANLL.NH 2 ) with MIC = 12.5 μM against Staphylococcus aureus and 50 μM against Escherichia coli . On the basis of similarities in morphology and advertisement calls, X. fraseri has been placed in a species group that includes the octoploids Xenopus amieti and Xenopus andrei , and the tetraploid Xenopus pygmaeus. Cladistic analyses based upon the primary structures of magainin, PGLa, and CPF-RP peptides support a close evolutionary relationship between X. fraseri , X. amieti and X. andrei but suggest a more distant relationship with X. pygmaeus .
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Host-defense peptides from skin secretions of the octoploid frogs Xenopus vestitus and Xenopus wittei (Pipidae): insights into evolutionary relationships.
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2014Co-Authors: Milena Mechkarska, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Katarzyna Michalak, Pawel Michalak, J. Michael ConlonAbstract:Abstract The primary structures of host-defense peptides have proved useful in elucidating the evolution history of frogs. Peptidomic analysis was used to compare the diversity of host-defense peptides in norepinephrine-stimulated skin secretions from the octoploid frogs, Xenopus vestitus (Kivu clawed frog) and Xenopus wittei (De Witte's clawed frog) in the family Pipidae. Structural characterization demonstrated that the X. vestitus peptides belong to the magainin (3 peptides), peptide glycine–leucine–amide (PGLa; 4 peptides), Xenopsin-precursor fragment (XPF; 1 peptide), and caerulein-precursor fragment (CPF; 5 peptides) families. The X. wittei peptides comprise magainin (4 peptides), PGLa (1 peptide), XPF (2 peptides), and CPF (7 peptides). In addition, secretions from both species contain caerulein, identical to the peptide from Xenopus laevis , but X. wittei secretions contains the novel peptide [R4K]Xenopsin. The variability in the numbers of paralogs in each peptide family indicates a selective silencing of the host-defense peptide genes following the polyploidization events. The primary structures of the peptides provide insight into phylogenetic relationships among the octoploid Xenopus frogs. The data support a sister-group relationship between X. vestitus and Xenopus lenduensis , suggestive of bifurcating speciation after allopolyploidization, whereas X. wittei is more closely related to the Xenopus amieti – Xenopus andrei group suggesting a common tetraploid ancestor. Consistent with previous data, the CPF peptides showed the highest growth inhibitory activity against bacteria with CPF-W6 (GIGSLLAKAAKLAAGLV.NH 2 ) combining high antimicrobial potency against Staphylococcus aureus (MIC = 4 μM) with relatively low hemolytic activity (LC 50 = 190 μM).
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Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae
Pharmaceuticals, 2014Co-Authors: J. Michael Conlon, Milena MechkarskaAbstract:Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and Xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored.
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Peptidomic analysis of skin secretions provides insight into the taxonomic status of the African clawed frogs Xenopus victorianus and Xenopus laevis sudanensis (Pipidae).
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2013Co-Authors: Jay D. King, Milena Mechkarska, Mohammed A Meetani, J. Michael ConlonAbstract:Peptidomic analysis was used to compare the distribution of host-defense peptides in norepinephrine-stimulated skin secretions from Xenopus victorianus Ahl, 1924 (also described as the subspecies X. laevis victorianus) and Xenopus laevis sudanensis Perret, 1966 with the previously determined distributions in Xenopus laevis (Daudin, 1802) and Xenopus petersii Bocage, 1895. Peptides belonging to the magainin, peptide glycine-leucine-amide (PGLa), and caerulein precursor fragment (CPF) families were purified by reversed-phase HPLC and characterized by electrospray mass spectrometry. Magainin-P2, PGLa-P1, CPF-P1, CPF-P2, and CPF-P3 previously isolated from X. petersii and structurally different from orthologous peptides from X. laevis, were identified in X. victorianus and X. laevis sudanensis skin secretions whereas the corresponding X. laevis peptides were absent. Magainin-1, identical in X. petersii and X. laevis, was also identified in the secretions. Xenopsin-precursor fragment (XPF) peptides, absent from X. petersii but present in X. laevis skin secretions, were not identified in the X. victorianus and X. laevis sudanensis secretions. The data indicate that X. victorianus and X. laevis sudanensis are more closely related to X. petersii than to X. laevis and support separate species status. The study illustrates the value of analysis of host-defense peptides in the evaluation of taxonomic and phylogenetic relationships between closely related frog species.
Robert E Carraway - One of the best experts on this subject based on the ideXlab platform.
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pro Xenopsin s in vesicles of mammalian brain liver stomach and intestine is apparently released into blood and cerebral spinal fluid
Regulatory Peptides, 2000Co-Authors: Robert E Carraway, Sankar P Mitra, David E. CochraneAbstract:Abstract Mammalian pro-Xenopsins (proXP), proteins (such as α-coatomer) that yield XP-related peptides when digested by pepsin-related proteases, are ubiquitously distributed in rats, with highest concentrations in liver and gastrointestinal tissues. Here, the cellular and subcellular distributions of canine and rat proXP were determined in brain, liver, stomach and intestine. Elutriation and percoll density centrifugation of collagenase-dispersed cells demonstrated that proXP was primarily associated with hepatocytes in liver, chief and parietal cells in stomach and endocrine/exocrine cells in intestine. When fragmented cells were subjected to differential centrifugation, ≅85% of proXP was associated with particulate fractions and only ≅15% was cytosolic. Sucrose-gradient centrifugation of crude mitochondrial preparations (P2 pellets) for liver, stomach and intestine demonstrated that proXP was localized to vesicles (density, ≅1.19; size, 80–400 μm), which contained material of variable electron density. In isotonic homogenates of brain, proXP migrated primarily with synaptosomes (density, ≅1.15) which contained vesicles (size, 50–100 μm). During HPLC-sizing and ion exchange chromatography, proXP gave at least three components, the major one being an anionic 140-kDa protein. ProXP-like activity was found in human and rat blood, human cerebral spinal fluid and in contents of the gastrointestinal lumen. These results are consistent with the idea that these vesicle-associated protein(s) could be released during endocrine and/or exocrine secretion and serve as precursors to XP-related peptides.
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Generation of Xenopsin-related peptides from tissue precursors by media conditioned by endotoxin-stimulated rat peritoneal macrophages
Inflammation, 1991Co-Authors: David E. Cochrane, Robert E Carraway, William BoucherAbstract:Incubation of media conditioned by endotoxin-stimulated rat peritoneal macrophages generates immunoreactive Xenopsin (iXP) when incubated with acid extracts of various tissues of the rat. The generation of iXP, as measured by specific radioimmunoassay and confirmed by HPLC analysis, increased as the length of the incubation period increased and was inhibited by pepstatin, prior boiling of the conditioned media, or by omitting either the tissue extract or the conditioned media. The pH optimum for the generation of iXP was 3.0. The generated iXP showed biological activity in that stimulated histamine secretion from isolated rat mast cells and this secretory response was prevented by metabolically poisoning the cells. In addition, the generated iXP stimulated contraction of the isolated guinea pig ileum. In this regard, it was similar to neurotensin (NT). Tissue precursor levels for iXP, as measured by this system of generation, were highest in kidney, liver, and skin and lowest in skeletal muscle and plasma. These results suggest to us that during the inflammatory response, the NT-related peptide, Xenopsin, can be generated from tissue precursor(s) by enzymes secreted by invading macrophages. The generated XP may then affect the participating cells of inflammation.
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Neurotensin elevates hematocrit and plasma levels of the leukotrienes, LTB4, LTC4, LTD4 and LTE4, in anesthetized rats.
Peptides, 1991Co-Authors: Robert E Carraway, Koutarou Muraki, David E. Cochrane, Rebecca Salmonsen, William BoucherAbstract:Abstract The IV injection of neurotensin (NT) into anesthetized rats produced a marked increase in hematocrit, labored breathing and peripheral blood stasis with cyanosis. This effect could also be produced by the NT-related peptides, neuromedin-N and Xenopsin; however, it was not observed when nine other biologically active peptides, including bradykinin and substance P, were tested. Associated with these responses were increases in the plasma levels of histamine (measured radioenzymatically) and the leukotrienes, LTB4, LTC4, LTD4, and LTE4 (measured by RIA and HPLC). The increment in hematocrit after varying doses of NT correlated to the increase in plasma levels of LTC4. Histamine and LTC4 were both capable of elevating hematocrit when given IV; however, LTC4 was ∼1000 times more potent than histamine and active doses of histamine elevated LTC4 levels. Furthermore, the effects of NT on plasma LTC4 and hematocrit were reduced by pretreating animals with antagonists to histamine and serotonin. Pretreatment with the specific mast cell degranulating agent, compound 48 80 , also blocked NT's ability to elevate plasma levels of histamine, LTB4 and LTC4 and prevented the increased hematocrit and cyanosis. These results indicate that NT-related peptides are very potent and specific stimulators of leukotriene release and that this action is mediated by mast cells and associated with loss of plasma volume and blood stasis. A working hypothesis is that histamine, released from mast cells in response to NT, stimulates LTC4 production by other cells.
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Xenopsin related peptide s are formed from Xenopsin precursor by leukocyte protease s and cathepsin d
Peptides, 1991Co-Authors: Robert E Carraway, Sankar P Mitra, Koutarou MurakiAbstract:Abstract Lysates of isolated rat polymorphonuclear leukocytes and macrophages were found to generate Xenopsin-related peptides when incubated with a liver extract used as a source of precursor. The lysosomal enzyme, cathepsin D, was also shown to display this property and to share with the lysate a similar pH dependence (optimum, ∼pH 3.5) and sensitivity to the acid protease inhibitor, pepstatin A (ID 50 : lysate, 10 nM; cathepsin D, 30 nM). When subjected to HPLC on μ-Bondapak C-18, the Xenopsin-related peptides generated by the lysate eluted near to those formed by cathepsin D and when tested in a radioreceptor assay for neurotensin, they displayed similar cross-reactivities (peak 2, ∼50%; peak 1, ∼100%). These results indicate that cathepsin D from lysed granulocytes can process precursor protein(s) to form radioreceptor-active Xenopsin-related peptides.
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isolation and structures of Xenopsin related peptides from rat stomach liver and brain
Regulatory Peptides, 1990Co-Authors: Robert E Carraway, Sankar P Mitra, Koutarou MurakiAbstract:Abstract Using radioimmunoassay for detection, a mammalian counterpart to amphibian Xenopsin (XP) was isolated and sequenced from pepsin-treated extracts of three different rat tissues and shown to be H-Phe-His-Pro-Lys-Arg-Pro-Trp-Ile-Leu-OH. This peptide, which shares six of the eight residues in XP, existed primarily in large molecular form(s) in the rat from which it could be liberated by the enzyme, pepsin. The XP-related sequence was differentially distributed through tissues, with concentrations ranging from ca. 80 pmol/g in diaphragm and skeletal muscle to ca. 800 pmol/g in stomach, liver and intestine. Like XP, the mammalian peptide potently crossreacted in a radioreceptor assay for neurotensin. These results prove the existence of radioreceptor-active XP-related sequences in multiple tissues of the rat.
Jane C. Kaltenbach - One of the best experts on this subject based on the ideXlab platform.
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Localization of Xenopsin and Xenopsin precursor fragment immunoreactivities in the skin and gastrointestinal tract of Xenopus laevis
Cell and Tissue Research, 1992Co-Authors: Kirsten C. Sadler, Charles L. Bevins, Jane C. KaltenbachAbstract:Xenopsin (Xp) and Xenopsin precursor fragment (XPF) are bioactive peptides derived from a single precursor molecule; both were isolated previously from extracts of Xenopus laevis skin. The present immunohistochemical study was undertaken to determine the specific cellular localization of these two peptides in the skin and also in the gastrointestinal tract of adult Xenopus . We report here that Xp-like and XPF-like immuno-reactivities co-exist in the granular glands of the skin and specific granular cells in the lower esophagus and stomach. However, only Xp-like immunoreactivity, not XPF-like immunoreactivity, was detected in tall, thin cells of the duodenum and in club-shaped cells of the large intestine. The immunochemical co-localization of the two peptides in specific cells of the skin, lower esophagus and stomach suggests that the same gene is expressed in each of these cells, and that the precursor molecule undergoes similar post-translational processing. In contrast, the observation that certain cells of the duodenum and large intestine display only one peptide immunoreactivity suggests an alternative phenomenon, possibly involving selective peptide accumulation or expression of a different gene.
Jay D. King - One of the best experts on this subject based on the ideXlab platform.
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Peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog Xenopus ruwenzoriensis (Pipidae)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2016Co-Authors: Laurent Coquet, Jolanta Kolodziejek, Norbert Nowotny, Thierry Jouenne, Jay D. King, J. Michael ConlonAbstract:Abstract The Uganda clawed frog Xenopus ruwenzoriensis with a karyotype of 2n = 108 is one of the very few vertebrates with dodecaploid status. Peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 6 peptides), Xenopsin precursor fragment (XPF; 3 peptides), caerulein precursor fragment (CPF; 8 peptides), and caerulein precursor fragment-related peptide (CPF-RP; 3 peptides). In addition, the secretions contained caerulein, identical to the peptide from Xenopus laevis , and two peptides that were identified as members of the trefoil factor family (TFF). The data indicate that silencing of the host-defense peptide genes following polyploidization has been appreciable and non-uniform. Consistent with data derived from comparison of nucleotide sequences of mitochrondrial and nuclear genes, cladistic analyses based upon the primary structures of the host-defense peptides provide support for an evolutionary scenario in which X. ruwenzoriensis arose from an allopolyploidization event involving an octoploid ancestor of the present-day frogs belonging to the Xenopus amieti species group and a tetraploid ancestor of Xenopus pygmaeus.
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Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).
Peptides, 2015Co-Authors: J. Michael Conlon, Milena Mechkarska, Jolanta Kolodziejek, Norbert Nowotny, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Jay D. KingAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), Xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation.
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Peptidomic analysis of skin secretions provides insight into the taxonomic status of the African clawed frogs Xenopus victorianus and Xenopus laevis sudanensis (Pipidae).
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 2013Co-Authors: Jay D. King, Milena Mechkarska, Mohammed A Meetani, J. Michael ConlonAbstract:Peptidomic analysis was used to compare the distribution of host-defense peptides in norepinephrine-stimulated skin secretions from Xenopus victorianus Ahl, 1924 (also described as the subspecies X. laevis victorianus) and Xenopus laevis sudanensis Perret, 1966 with the previously determined distributions in Xenopus laevis (Daudin, 1802) and Xenopus petersii Bocage, 1895. Peptides belonging to the magainin, peptide glycine-leucine-amide (PGLa), and caerulein precursor fragment (CPF) families were purified by reversed-phase HPLC and characterized by electrospray mass spectrometry. Magainin-P2, PGLa-P1, CPF-P1, CPF-P2, and CPF-P3 previously isolated from X. petersii and structurally different from orthologous peptides from X. laevis, were identified in X. victorianus and X. laevis sudanensis skin secretions whereas the corresponding X. laevis peptides were absent. Magainin-1, identical in X. petersii and X. laevis, was also identified in the secretions. Xenopsin-precursor fragment (XPF) peptides, absent from X. petersii but present in X. laevis skin secretions, were not identified in the X. victorianus and X. laevis sudanensis secretions. The data indicate that X. victorianus and X. laevis sudanensis are more closely related to X. petersii than to X. laevis and support separate species status. The study illustrates the value of analysis of host-defense peptides in the evaluation of taxonomic and phylogenetic relationships between closely related frog species.
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Host-defense peptides in skin secretions of the tetraploid frog Silurana epitropicalis with potent activity against methicillin-resistant Staphylococcus aureus (MRSA).
Peptides, 2012Co-Authors: J. Michael Conlon, Milena Mechkarska, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Manju Prajeep, Agnes Sonnevend, Jay D. KingAbstract:Abstract A putative genome duplication event within the Silurana lineage has given rise to the tetraploid Cameroon clawed frog Silurana epitropicalis (Fischberg, Colombelli, and Picard, 1982). Peptidomic analysis of norepinephrine-stimulated skin secretions of S. epitropicalis led to identification of 10 peptides with varying degrees of growth-inhibitory activity against Escherichia coli and Staphylococcus aureus . Structural characterization identified the peptides as belonging to the magainin family (magainin-SE1), the caerulein-precursor fragment family (CPF-SE1, -SE2 and -SE3), the Xenopsin-precursor fragment family (XPF-SE1, SE-2, SE-3 and -SE4), and the peptide glycine-leucine-amide family (PGLa-SE1 and -SE2). In addition, peptide phenylalanine-glutamine-amide (FLGALLGPLMNLLQ·NH 2 ) was isolated from the secretions that lacked antimicrobial activity. Comparison of the multiplicity of orthologous peptides in S. epitropicalis and the diploid Silurana tropicalis indicates that extensive nonfunctionalization (deletion or silencing) of antimicrobial peptide genes has occurred after polyploidization in the Silurana lineage, as in the Xenopus lineage. CPF-SE2 (GFLGPLLKLGLKGAAKLLPQLLPSRQQ; MIC = 2.5 μM) and CPF-SE3 (GFLGSLLKTGLKVGSNLL·NH 2 ; MIC = 5 μM) showed potent growth-inhibitory activity against a range of clinical isolates of methicillin-resistant S. aureus (MRSA). Their utility as systemic anti-infective drugs is limited by significant hemolytic activity against human erythrocytes (LC 50 = 50 μM for CPF-SE2 and 220 μM for CPF-SE3) but the peptides may find application as topical agents in treatment of MRSA skin infections and decolonization of MRSA carriers.
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Host-defense peptides from skin secretions of the tetraploid frogs Xenopus petersii and Xenopus pygmaeus, and the octoploid frog Xenopus lenduensis (Pipidae)
Peptides, 2011Co-Authors: Jay D. King, Milena Mechkarska, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Hubert Vaudry, Koji Takada, J. Michael ConlonAbstract:Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions led to the identification of host-defense peptides belonging to the magainin, peptide glycine-leucine-amide (PGLa), and caerulein precursor fragment (CPF) families from the tetraploid frogs, Xenopus petersii (Peters’ clawed frog) and Xenopus pygmaeus (Bouchia clawed frog), and the octoploid frog Xenopus lenduensis (Lendu Plateau clawed frog). Xenopsin-precursor fragment (XPF) peptides were not detected. The primary structures of the antimicrobial peptides from X. petersii demonstrate a close, but not conspecific relationship, with Xenopus laevis whereas the X. pygmaeus peptides show appreciable variation from previously characterized orthologs from other Xenopus species. Polyploidization events within the Xenopodinae ( Silurana + Xenopus ) are associated with extensive gene silencing (nonfunctionization) but unexpectedly the full complement of four PGLa paralogs were isolated from X. lenduendis secretions. Consistent with previous data, the CPF peptides showed the highest growth-inhibitory activity against bacteria with CPF-PG1 (GFGSLLGKALKIGTNLL.NH 2 ) from X. pygmaeus combining high antimicrobial potency against Staphylococcus aureus (MIC = 6 μM) with relatively low hemolytic activity (LC 50 = 145 μM).
