RSSAirway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells.
Source
Department of Life Science, Pohang University of Science and Technology Biotech Center, Pohang 790-784, Republic of Korea.
Abstract
Formyl peptide receptors (FPRs) are chemoattractant receptors that mediate inflammatory cell responses to infection. Recent evidence indicates that noneosinophilic asthma phenotypes can be developed by both Th1 and Th17 cell responses when exposed to LPS-containing allergens. In this study, we evaluated the effects of airway activation of FPRs by their synthetic agonist, Trp-Lys-Tyr-Met-Val-D-Met (W-peptide), on the development of Th1 and Th17 cell responses in a noneosinophilic asthma mouse model. A noneosinophilic asthma mouse model was generated by intranasal sensitization with 10 μg of LPS plus 75 μg of OVA on days 0, 1, 2, and 7. Mice were then challenged with 50 μg of OVA alone on days 14, 15, 21, and 22. W-peptide was administered during the sensitization period, and immune and inflammatory responses were evaluated after OVA challenge. Lung inflammation after OVA challenge was partly abolished by airway activation of FPRs during sensitization. Maturation of dendritic cells (DCs) and migration of DCs from the lung to lung-draining lymph nodes were inhibited by FPR activation. In addition, airway activation of FPRs inhibited allergen-specific T cell proliferation in the lymph nodes. Production of IL-12 and IL-6 (Th1- and Th17-polarizing cytokines) from lung DCs was decreased by airway activation of FPRs. This effect resulted in the inhibition of allergen-specific Th1 and Th17 cell responses. Airway activation of FPRs during sensitization effectively prevents the development of Th1 and Th17 cell responses induced by LPS-containing allergens via multiple mechanisms, such as inhibition of DC maturation and migration and the production of Th1- and Th7-polarizing cytokines.
- PMID:
- 22262660
- [PubMed - as supplied by publisher]
A universal strategy for preparing protected C-terminal peptides on the solid phase through an intramolecular click chemistry-based handle.
Source
Institute for Research in Biomedicine, Barcelona Science Park (PCB), Baldiri Reixac 10, 08028-Barcelona, Spain. albericio@irbbarcelona.org judit.tulla@irbbarcelona.org.
Abstract
A new universal strategy exploits DKP formation in a dipeptide moiety whose C-terminal residue is blocked by a leaving group. It enables both synthesis of C-terminal protected peptides that are useful for convergent synthesis of large peptides and use of a C-terminal permanent protecting group that can be cleaved by catalytic hydrogenation to release the peptide.
- PMID:
- 22262473
- [PubMed - as supplied by publisher]
[Construction and toxicity the recombinant SpltMNPV expressing the scorpion toxin gene].
Source
School of Biology and Basic Medical Science, Medical College of Soochow University, Suzhou 215123, China. alicetangsz@yahoo.com.cn
Abstract
OBJECTIVE:
To develop a high toxic recombinant Spodoptera litura multicapsid nucleopolyhedroviruse (SpltMNPV) insecticide.
METHODS:
We constructed a recombinant transfer vector that was characterized by disrupting of ecdysterioid UDP-glucosyltransferase (egt) gene and expressing the mature peptide of the Chinese scorpion, B. martensi Karsch (BmK ITal) gene at the control of ie-1 promoter. The transfer vector and the SpltMNPV II DNA cotransfected the SpLi cells. Recombinant viruses were purified by the end point dilution and fluorescent spot purification.
RESULTS:
We successfully screened the recombinant SpltMNPV-deltaegt-Pph-egfp-ie-1-BmK ITal of which the egt gene was knocked out and expressed the mature peptide of the BmK ITal gene at the control of ie-1 promoter. Bioassays showed that, compared to the wide-type SpltMNPV, the speed of the recombinant virus killing the S. litura (LT50) increased by 0.7-0.8 days.
CONCLUSION:
The insecticidal effect of SpltNPV could be increased by inserting the foreign gene, which provided a further opportunity to develop the SpltNPV into commercially viable products to control the S. litura.
- PMID:
- 22260048
- [PubMed - in process]
Beverage consumption, appetite, and energy intake: what did you expect?
Source
Department of Nutrition Science, Purdue University, West Lafayette, IN, and the Department of Medicine, Indiana University, Indianapolis, IN.
Abstract
BACKGROUND:
Beverage consumption is implicated in the overweight/obesity epidemic through the weaker energy compensation response it elicits compared with solid food forms. However, plausible mechanisms are not documented.
OBJECTIVE:
This study assessed the cognitive and sensory contributions of differential postingestive responses to energy- and macronutrient-matched liquid (in beverage form) and solid food forms and identifies physiologic processes that may account for them.
DESIGN:
Fifty-two healthy adults [mean ± SD age: 24.7 ± 5.5 y; BMI (in kg/m(2)): 26.3 ± 6.3] completed this randomized, 4-arm crossover study. Participants consumed oral liquid and solid preloads that they perceived, through cognitive manipulation, to be liquid or solid in their stomach (ie, oral liquid/perceived gastric liquid, oral liquid/perceived gastric solid, oral solid/perceived gastric liquid, or oral solid/perceived gastric solid). However, all preloads were designed to present a liquid gastric challenge. Appetite, gastric-emptying and orocecal transit times, and selected endocrine responses were monitored for the following 4 h; total energy intake was also recorded.
RESULTS:
Oral-liquid and perceived gastric-liquid preloads elicited greater postprandial hunger and lower fullness sensations, more rapid gastric-emptying and orocecal transit times, attenuated insulin and glucagon-like peptide 1 release, and lower ghrelin suppression than did responses after oral-solid and perceived gastric-solid treatments (all P < 0.05). Faster gastric-emptying times were significantly associated with greater energy intake after consumption of perceived gastric-liquid preloads (P < 0.05). Energy intake was greater on days when perceived gastric-liquid preloads were consumed than when perceived gastric solids were consumed (2311 ± 95 compared with 1897 ± 72 kcal, P = 0.007).
CONCLUSIONS:
These data document sensory and cognitive effects of food form on ingestive behavior and identify physical and endocrine variables that may account for the low satiety value of beverages. They are consistent with findings that clear, energy-yielding beverages pose a particular risk for positive energy balance. This study is registered at clinicaltrials.gov as NCT01070199.
Synthesis, evaluation and molecular modeling of cyclic tetrapeptide histone deacetylase inhibitors as anticancer agents.
Source
School of Life Science and Biotechnology, Dalian University of Technology, Dalian, 116024, China.
Abstract
Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(-l-Am7(S2Py)-Aib-l-Phe(n-Me)-d-Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three human cancer cell lines with IC(50) in the micromolar range. Docking and molecular dynamics simulation were conducted to explore the interaction mechanisms of class I and II HDACs with these inhibitors. It revealed that the zinc ion in the active site coordinated five atoms of HDACs and the sulfur atom of the inhibitor. The metal binding domains of these compounds interacted with HDAC2, and the surface recognition domains of these compounds interacted with HDAC4 through hydrogen bonding. The hydrophobic interactions also provided favorable contributions to stabilize the complexes. The results obtained from this study would be helpful for us to design some novel cyclic tetrapeptides that may act as potent HDACIs. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Running throughout middle-age improves memory function, hippocampal neurogenesis and BDNF levels in female C57Bl/6J mice.
Source
Swammerdam Institute for Life Science - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, 21224, USA.
Abstract
Age-related memory loss is considered to commence at middle-age and coincides with reduced adult hippocampal neurogenesis and neurotrophin levels. Consistent physical activity at midlife may preserve brain-derived neurotrophic factor (BDNF) levels, new cell genesis and learning. In the present study, 9-month-old female C57Bl/6J mice were housed with or without a running wheel and injected with bromodeoxyuridine (BrdU) to label newborn cells. Morris water maze learning, open field activity and rotarod behavior were tested 1 and 6 months after exercise onset. Here we show that long-term running improved retention of spatial memory and modestly enhanced rotarod performance at 15 months of age. Both hippocampal neurogenesis and mature BDNF peptide levels were elevated after long-term running. Thus, regular exercise from the onset and during middle-age may maintain brain function. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012.
Copyright © 2012 Wiley Periodicals, Inc.
Comment on "binding free energies of inhibitors to iron porphyrin complex as a model for cytochrome p450".
Source
Department of Molecular Drug Research, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen 2100, Denmark. pry@farma.ku.dk.
Enhanced cellular uptake and metabolic stability of lipo-oligoarginine peptides.
Source
Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX 77030.
Abstract
Developing efficient cellular delivery vectors is crucial for designing novel therapeutic agents to enhance their plasma membrane permeability and metabolic stability in cells. Previously, we engineered cell penetrating peptide vectors named as "lipo-oligoarginine peptides" (LOAPs) by conjugating a proper combination of fatty acid and oligoarginine that translocated into cell easily without adverse effect on cell viability. In the present study, we report a systemic evaluation of cellular uptake and metabolic stability of LOAPs in Jurkat cells by introducing different combination of D-Arg residues in the peptide backbone. The cellular uptake and intracellular fate, cell viability, and metabolic stability and proteolytic degradation patterns of various LOAPs consisted of different combination of L- and D-Arg sequences were confirmed by flow cytometry, cytotoxicity assay, and analytical RP-HPLC with MALDI-TOF mass. All investigated LOAPs penetrated the cell efficiently with low cellular toxicity. The LOAPs having D-Arg residues at their N-termini seemed to have better metabolic stability than the LOAPs having C-terminal D-Arg residues. The metabolic degradation patterns were similar among all investigated LOAPs. The major hydrolytic site was between lauroyl group and β-Ala residue. Without the lipid chain, the oligoarginine peptide was pumped out ofcells easily. The results presented in this study suggest that structurally modified LOAPs could be used as a novel CPP design toward improved therapeutic application. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 772-779, 2011.
Copyright © 2011 Wiley Periodicals, Inc.
Chain length effects on helix-hairpin distribution in short peptides with Aib-(D) Ala and Aib-Aib Segments.
Source
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Abstract
The Aib-(D) Ala dipeptide segment has a tendency to form both type-I'/III' and type-I/III β-turns. The occurrence of prime turns facilitates the formation of β-hairpin conformations, while type-I/III turns can nucleate helix formation. The octapeptide Boc-Leu-Phe-Val-Aib-(D) Ala-Leu-Phe-Val-OMe (1) has been previously shown to form a β-hairpin in the crystalline state and in solution. The effects of sequence truncation have been examined using the model peptides Boc-Phe-Val-Aib-Xxx-Leu-Phe-NHMe (2, 6), Boc-Val-Aib-Xxx-Leu-NHMe (3, 7), and Boc-Aib-Xxx-NHMe (4, 8), where Xxx = (D) Ala, Aib. For peptides with central Aib-Aib segments, Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe (6), Boc-Val-Aib-Aib-Leu-NHMe (7), and Boc-Aib-Aib-NHMe (8) helical conformations have been established by NMR studies in both hydrogen bonding (CD(3) OH) and non-hydrogen bonding (CDCl(3) ) solvents. In contrast, the corresponding hexapeptide Boc-Phe-Val-Aib-(D) Ala-Leu-Phe-Val-NHMe (2) favors helical conformations in CDCl(3) and β-hairpin conformations in CD(3) OH. The β-turn conformations (type-I'/III) stabilized by intramolecular 4→1 hydrogen bonds are observed for the peptide Boc-Aib-(D) Ala-NHMe (4) and Boc-Aib-Aib-NHMe (8) in crystals. The tetrapeptide Boc-Val-Aib-Aib-Leu-NHMe (7) adopts an incipient 3(10) -helical conformation stabilized by three 4→1 hydrogen bonds. The peptide Boc-Val-Aib-(D) Ala-Leu-NHMe (3) adopts a novel α-turn conformation, stabilized by three intramolecular hydrogen bonds (two 4→1 and one 5→1). The Aib-(D) Ala segment adopts a type-I' β-turn conformation. The observation of an NOE between Val (1) NH↔HNCH(3) (5) in CD(3) OH suggests, that the solid state conformation is maintained in methanol solutions. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 744-756, 2011.
Copyright © 2011 Wiley Periodicals, Inc.
Sol and gel states in peptide hydrogels visualized by Gd(III)-enhanced magnetic resonance imaging.
Source
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112.
Abstract
The hydrogels assembled from a pair of self-repulsive but mutually attractive decapeptides are visualized by magnetic resonance imaging (MRI). It is found that in the absence of Gd(III)-chelate, gelation has little effect on MRI signal intensity. In the presence of Gd(III)-chelate, gelation leads to significant changes in water relaxation and MR signal intensity. The sol to gel transition is best visualized by T(2) -weighted imaging using large echo time with the sol producing a bright spot and the gel producing a dark spot. MRI studies point to high local Gd(III)-chelate concentration. Small-angle X-ray scattering study indicates that this local enrichment of Gd(III)-chelate has two contributing processes: first, the aggregation of peptides into fibers; second, within peptide fibers, Gd(III)-chelate further aggregate into clusters. This work demonstrates that the status of peptide-based hydrogels can be visualized by MRI with the aid of covalently linked Gd(III)-chelates. This result has implications for monitoring peptide scaffolds in vivo. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 734-743, 2011.
Copyright © 2011 Wiley Periodicals, Inc.
The silkmoth eggshell as a natural amyloid shield for the safe development of insect oocyte and embryo: Insights from studies of silkmoth chorion proteinpeptide-analogues of the B famil.
Source
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece.
Abstract
Silkmoth chorion is the major component of the silkmoth eggshell. The proteins that constitute more than 95% of its dry mass have remarkable mechanical and physicochemical properties forming a protective natural shield for the oocyte and the developing embryo from a wide range of environmental hazards. Peptide-analogues of the central conservative domain of the two major families of silkmoth chorion proteins, the A's and the B's, form amyloid fibrils under a variety of conditions, which prompted us to propose, 10 years ago, that silkmoth chorion is an amyloid with protective properties. Following our finding, a number of studies verified the existence of several functional amyloids. In this study, we designed, synthesized and studied two peptide-analogues of the central conservative domain of the B family of silkmoth chorion proteins, and we present experimental results, which show: (a) that the amyloidogenic properties of silkmoth chorion peptides are encoded into the tandemly repeating hexapeptides comprising the central domain of silkmoth chorion proteins, confirming our previous findings from peptide analogues of the A family of chorion proteins, and, (b) they suggest how silkmoth chorion proteins of the B family self-assemble in vivo, for the formation of the helicoidal architecture of silkmoth chorion. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 723-733, 2011.
Copyright © 2011 Wiley Periodicals, Inc.
A convenient approach to synthesizing peptide C-terminal N-alkyl amides.
Source
Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045.
Abstract
Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptideC-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the peptide amide linker-polyethylene glycol-polystyrene (PAL-PEG-PS) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 715-722, 2011.
Copyright © 2011 Wiley Periodicals, Inc.
Dose-response effects of an antimicrobial peptide, a cecropin hybrid, on growth performance, nutrient utilisation, bacterial counts in the digesta and intestinal morphology in broilers.
Source
School of Life Science, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.
Abstract
The aim of the present study was to evaluate the feasibility of an antimicrobial peptide, cecropin A(1-11)-D(12-37)-Asn (CADN), as an alternative to antibiotic growth promoter (AGP) in poultry diets. A total of 1500 14-d-old indigenous male chickens (222 (sd 13) g) were randomly allocated to five groups with five replicate cages of sixty birds each, and fed ad libitum five grower diets and subsequently five finisher diets for 14 d each. The diets were made up by supplementing their basal diets with a CADN liquid sample (CADNL) at 0, 2, 4, 6 and 8 ml/kg, respectively. During the feeding period, a metabolic experiment was carried out to determine the apparent digestibility of diethyl ether extract, nitrogen retention and apparent metabolisable energy of the diet sample fed to each cage of chicks. At the end of the feeding experiment, one chick from each cage was killed for bacteriological, light microscopic and scanning electron microscopic examination of the intestinal villi. CADN had a negative linear, positive quadratic and negative linear effect on feed intake (F), weight gain (G) and feed:gain ratio (F:G), respectively, for the growers; it had a quadratic effect on F, G or F:G for the finishers; it increased nutrient utilisation for both growers and finishers; it decreased aerobic bacterial counts in both jejunal and caecal digesta in a dose-dependent manner; it enhanced intestinal villus heights in a dose-dependent manner and made the duodenum villi of the CADNL8 group at 42 d appear as a netted leaf-like structure. CADN is therefore a possible alternative to AGP in broiler feeds.
Leptin receptors.
Source
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, EH16 4TH, UK.
Abstract
The hormone leptin, secreted predominantly from adipose tissue, plays a crucial role in the regulation of numerous neuroendocrine functions, from energy homeostasis to reproduction. Genetic deficiency as a consequence of leptin or leptin receptor mutations, although rare in humans, leads to early onset of chronic hyperphagia and massive obesity. In most human obesity, however, leptin levels are chronically elevated. Under these conditions of persistent hyperleptinaemia, and particularly when obesity is associated with a high-fat diet, leptin resistance develops, and signalling through the leptin receptor is curtailed, fuelling further weight gain. Here, we review the role of leptin receptors in the regulation of feeding and obesity development. Leptin receptors are found in each of the major components of the CNS "feeding" circuitry-the brainstem, hypothalamus and distributed reward centres. Through these receptors, leptin exerts influences on signalling and integration within these circuits to alter feeding behaviours. Although some progress is now being made with peptide analogues, the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date. Where clinical benefit from recombinant leptin administration has been achieved, this has been under circumstances of complete endogenous leptin deficiency or relative hypoleptinaemia such as in lipodystrophy.
Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner.
Source
1] Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China [2] Department of Psychology, School of Art and Science University of Pennsylvania, Philadelphia, PA, USA.
Abstract
Background:The physiological control of feeding behavior involves modulation of the intake inhibitory effects of gastrointestinal satiation signaling via endogenous hindbrain leptin receptor (LepR) and glucagon-like-peptide-1 receptor (GLP-1R) activation.Design and Results:Using a variety of dose-combinations of hindbrain delivered (4th intracerebroventricular; i.c.v.) leptin and the GLP-1R agonist exendin-4, experiments demonstrate that hindbrain LepR and GLP-1R signaling interact to control food intake and body weight in an additive manner. In addition, the maximum intake suppressive response that could be achieved by 4th i.c.v. leptin alone in non-obese rats (∼33%) was shown to be further suppressed when exendin-4 was co-administered. Importantly, it was determined that the interaction between hindbrain LepR signaling and GLP-1R signaling is relevant to endogenous food intake control, as hindbrain GLP-1R blockade by the selective antagonist exendin-(9-39) attenuated the intake inhibitory effects of hindbrain leptin delivery.Conclusions:Collectively, the findings reported here show that hindbrain LepR and GLP-1R activation interact in at least an additive manner to control food intake and body weight. As evidence is accumulating that combination pharmacotherapies offer greater sustained food intake and body weight suppression in obese individuals when compared with mono-drug therapies or lifestyle modifications alone, these findings highlight the need for further examination of combined central nervous system GLP-1R and LepR signaling as a potential drug target for obesity treatment.International Journal of Obesity advance online publication, 17 January 2012; doi:10.1038/ijo.2011.265.
Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse.
Source
Texas Christian University, College of Science and Engineering, Department of Psychology, 2800 S. University Drive, Fort Worth, TX 76129, USA.
Abstract
Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of Aβ1-42, apeptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased Aβ1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased Aβ1-42 in the hippocampus and cognitive deficits in mice.
Copyright © 2012. Published by Elsevier B.V.
The use of antiendotoxin peptides in obstructive jaundice endotoxemia.
Source
Department of Surgery, Institute of Clinical Science, Queens University Belfast, Belfast, UK.
Abstract
BACKGROUND:
Two novel antiendotoxin peptides, P6 and C1, may reduce the inflammatory response. This study aimed to determine the effect of endotoxin on hepatic cytokine response and to assess P6 and C1-related attenuation of the proinflammatory response to endotoxemia, in experimental biliary obstruction.
MATERIALS AND METHODS:
15 Male Wistar rats were randomized to one of three groups: bile duct ligation (BDL)+P6 (n=5), BDL+C1 (n=5), and BDL+no peptide (n=5). Rats were weighed and underwent BDL surgery on day 1. On day 8, the rats were reweighed and isolated hepatic perfusion was carried out. P6 or C1 peptide (10 μmol/l) was preincubated with 300 ml of endotoxin-containing Krebs perfusate. After perfusion of 10 min with endotoxin-free perfusate, the livers were perfused for another 10 min with 300 ml of perfusate-containing endotoxin on its own or endotoxin plus peptide. This was followed by a further 100 min of perfusion with endotoxin-free perfusate. Effluent perfusate was collected at 20-min intervals for subsequent biochemical and cytokine analyses.
RESULTS:
Perfusion with endotoxin+P6 or endotoxin+C1 resulted in no significant difference in weight loss, or interleukin-6 response compared with perfusion with endotoxin alone. However, perfusion with endotoxin+P6 or endotoxin+C1 significantly reduced the tumor necrosis factor-α response to portal endotoxemia compared with perfusion with endotoxin alone.
CONCLUSION:
This study demonstrates that novel antiendotoxin peptides may attenuate the hepatic inflammatory response in portal endotoxemia. In obstructive jaundice, preoperative peptide administration may reduce endotoxin-related postoperative complications.
- PMID:
- 22246330
- [PubMed - as supplied by publisher]
Turkish scorpion Buthacus macrocentrus: General characterization of the venom and description of Bu1, a potent mammalian Na(+)-channel α-toxin.
Source
Department of Biology, Faculty of Science and Art, Eskisehir Osmangazi University, 26480 Eskisehir, Turkey; Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, UNAM, Av. Universidad, 2001, Col. Chamilpa, Apartado Postal 510-3, Cuernavaca, Morelos 62210, Mexico.
Abstract
The venom of the scorpion Buthacus macrocentrus of Turkey was fractionated by high performance liquid chromatography (HPLC) and its mass finger print analysis was obtained by spectrometry. More than 70 different fractions were obtained, allowing the determination of the molecular masses of at least 60 peptides ranging between 648 and 44,336 Da. The venom is enriched with peptides containing molecular masses between 3200-4500 Da, and 6000-7500 Da. They very likely correspond to K(+)-channel and Na(+)-channel specific peptides, respectively, as expected from venoms of scorpions of the family Buthidae, already determined for other species. The major component obtained from HPLC was shown to be lethal to mice and was further purified and characterized. It contains 65 amino acid residues maintained closely packed by 4 disulfide bridges, and shows a molecular weight of 7263 Da. Additionally, a cDNA from the venomous glands of this scorpion was used in conjunction with sequence data from Edman degradation and mass spectrometry for cloning the gene that codes for Bu1 as we named this toxin. This gene codes for a 67 amino acid residues peptide, where the two last are eliminated post-translationally for production of an amidated C-terminal arginine. Its sequence is closely related to toxins from the species Leiurus quinquestriatus, as revealed by a phylogenetic tree analysis. Electrophysiological results conducted with Bu1 using patch-clamp techniques indicate that it modifies the Na(+) currents, in a similar way as other well known α-scorpion toxins. These results support the conclusion that this species of scorpions is dangerous to humans, having an epidemiological interest for the country.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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