APITOXINA & ANTIBIOTICO
| Items 1 - 48 of 48 |
| 1: Antimicrob Agents Chemother. 2005 Oct;49(10):4085-92. |
Atomic force
microscopy study of the effect of antimicrobial peptides on the cell envelope
of Escherichia coli.
Meincken
M, Holroyd
DL, Rautenbach
M.
UNESCO Associated Centre for Macromolecules, Department of Chemistry,
The influences of the antibacterial magainin 2 and PGLa from the African clawed
frog (Xenopus laevis) and the hemolytic bee venom melittin on Escherichia
coli as the target cell were studied by atomic force microscopy (AFM). Nanometer-scale
images of the effects of the peptides on this gram-negative bacterium's cell
envelope were obtained in situ without the use of fixing agents. These high-resolution
AFM images of the surviving and intact target cells before and after peptide
treatment showed distinct changes in cell envelope morphology as a consequence
of peptide action. Although all three peptides are lytic to E. coli, it is
clear from this AFM study that each peptide causes distinct morphological
changes in the outer membrane and in some cases the inner membrane, probably
as a consequence of different mechanisms of action.
| 2: FEBS Lett. 2005 Mar 14;579(7):1658-64. |
Cross-presentation
of a CMV pp65 epitope by human dendritic cells using bee venom PLA2 as a membrane-binding
vector.
Babon A, Almunia C, Boccaccio C,
Beaumelle B,
Gelb MH, Menez A, Maillere B, Abastado JP,
Salcedo M, Gillet D.
Protein Engineering and Research
Department (DIEP), bat 152, CEA-Saclay, 91191 Gif sur Yvette cedex,
We have used bee venom phospholipase A2 as a vector to load human dendritic
cells ex vivo with a major histocompatibility complex (MHC) class I-restricted
epitope fused to its C-terminus. The fusion protein bound to human monocyte-derived
dendritic cells and was internalized into early endosomes. In vitro immunization
experiments showed that these dendritic cells were able to generate specific
CD8 T cell lines against the epitope carried by the fusion protein. Cross-presentation
did not require proteasome, transporter associated with antigen processing,
or endosome proteases, but required newly synthesized MHC molecules. Comparison
of the antigen presentation pathway observed in this study to that followed
by other toxins used as vectors is discussed.
| 3: Peptides. 2005 Feb;26(2):217-25. |
Conformation
and activity of delta-lysin and its analogs.
Dhople
VM, Nagaraj
R.
Centre for Cellular and Molecular Biology,
Delta-Lysin is a 26-residue hemolytic peptide secreted by Staphylococcus aureus.
Unlike the bee venom peptide melittin, delta-lysin does not exhibit antibacterial
activity. We have synthesized delta-lysin and several analogs wherein the
N-terminal residues of the toxin were sequentially deleted. The toxin has
three aspartic acids, four lysines and no prolines. Analogs were also generated
in which all the aspartic acids were replaced with lysines. A proline residue
was introduced in the native sequences as well as in the analogs where aspartic
acids were replaced with lysines. We observed that 20- and 22-residue peptides
corresponding to residues 7-26 and 5-26 of delta-lysin, respectively, had
greater hemolytic activity than the parent peptide. These shorter peptides,
unlike delta-lysin, did not self-associate to adopt alpha-helical conformation
in water, at lytic concentrations. Introduction of proline or substitution
of aspartic acids by lysines resulted in loss in propensity to adopt helical
conformation in water. When proline was introduced in the peptides corresponding
to the native toxin sequence, loss of hemolytic activity was observed. Substitution
of all the aspartic acids with lysines resulted in enhanced hemolytic activity
in all the analogs. However, when both proline and aspartic acid to lysine
changes were made, only antibacterial activity was observed in the shorter
peptides. Our investigations on delta-lysin and its analogs provide insights
into the positioning of anionic, cationic residues and proline in determining
hemolytic and antibacterial activities.
| 4: J Vet Sci. 2001 Aug;2(2):121-4. |
Therapeutic
effect of bee venom in sows with hypogalactia syndrome postpartum.
Choi
SH, Kang
SS.
Department of Veterinary Surgery, College of Veterinary Medicine and Research
Institute of Veterinary Medicine, Chungbuk National University, Cheongju 361-763,
Korea. shchoi@cbucc.chungbuk.ac.kr
The objective of this study was to determine the clincotherapeutic effect
of whole bee venom in hypogalactic sows postpartum. Sows after parturition
were assigned to treated and nontreated control groups. In the treated group,
22 sows were bee acupunctured once a day for 3 consecutive days. Honeybees
(Apis mellifera L.) for bee acupuncture were about 15 days after metamorphosis.
One live bee was used to sting the acupoints known as Yang-ming (ST-18,
PMID: 14614282 [PubMed - indexed for MEDLINE]
| 5: Am J Chin Med. 2003;31(1):149-55. |
Effect of
bee venom treatment in sows with oligogalactic syndrome postpartum.
Choi
SH, Kang
SS, Bae
CS, Cho
SK, Pak
SC.
The objective of this study was to determine the clinico-therapeutic effect
of worker honeybee venom in sows with oligogalactic syndrome postpartum. Comparison
between bee venom- and drug-treated groups was our main concern in the present
study. Sows after parturition were assigned to bee venom- and drug-treated
groups, respectively. In the bee venom-treated group, 22 sows were bee-acupunctured
once a day for 3 consecutive days. Honeybees (Apis mellifera L.) forbee acupuncture
were about 15 days old after metamorphosis. Live bees were used to sting the
acupoints known as yang-ming (ST-18,
PMID: 12723765 [PubMed - indexed for MEDLINE]
| 6: Antimicrob Agents Chemother. 2003 Mar;47(3):965-71. |
Modulation
of the activity of secretory phospholipase A2 by antimicrobial peptides.
Zhao
H, Kinnunen
PK.
Helsinki Biophysics & Biomembrane Group, Institute of Biomedicine, FIN-00014
The antimicrobial peptides magainin 2, indolicidin, and temporins B and L
were found to modulate the hydrolytic activity of secretory phospholipase
A(2) (sPLA(2)) from bee venom and in human lacrimal fluid. More specifically,
hydrolysis of phosphatidylcholine (PC) liposomes by bee venom sPLA(2) at 10
micro M Ca(2+) was attenuated by these peptides while augmented product formation
was observed in the presence of
| 7: Chembiochem. 2002 Jul 2;3(7):664-71. |
Erratum in:
· Chembiochem. 2002 Aug 29;3(8):687.
Molecular basis
of phospholipase A2 inhibition by petrosaspongiolide M.
Dal Piaz F, Casapullo A,
Randazzo A, Riccio R, Pucci P, Marino G, Gomez-Paloma L.
Dipartimento di Chimica Organica e Biochimica Universita di Napoli Federico
II via Cinthia 6, 80126 Napoli, Italy.
Petrosaspongiolide M (PM) is
an anti-inflammatory marine metabolite that displays a potent inhibitory activity
toward group II and III secretory phospholipase A(2) (PLA(2)) enzymes. The
details of the mechanism, which leads to a covalent adduct between PLA(2)
and gamma-hydroxybutenolide-containing molecules such as PM, are still a matter
of debate. In this paper the covalent binding of PM to bee venom PLA(2) has
been investigated by mass spectrometry and molecular modeling. The mass increment
observed for the PM-PLA(2) adduct is consistent with the formation of a Schiff
base by reaction of a PLA(2) amino group with the hemiacetal function (masked
aldehyde) at the C-25 atom of the PM gamma-hydroxybutenolide ring. Proteolysis
of the modified PLA(2) by the endoprotease LysC followed by HPLC MS analysis
allowed us to establish that the PLA(2) alpha-amino terminal group of the
Ile-1 residue was the only covalent binding site for PM. The stoichiometry
of the reaction between PM and PLA(2) was also monitored and results showed
that even with excess inhibitor, the prevalent product is a 1:1 (inhibitor:enzyme)
adduct, although a 2:1 adduct is present as a minor component. The 2:1 adduct
was also characterized, which showed that the second site of reaction is located
at the epsilon -amino group of the Lys-85 residue. Similar results in terms
of the reaction profile, mass increments, and location of the PLA(2) binding
site were obtained for manoalide, a paradigm for irreversible PLA(2) inhibitors,
which suggests that the present results may be considered of more general
interest within the field of anti-inflammatory sesterterpenes that contain
the gamma-hydroxybutenolide pharmacophore. Finally, a 3D model, constrained
by the above experimental results, was obtained by docking the inhibitor molecule
into the PLA(2) binding site through AFFINITY calculations. The model provides
an interesting insight into the PM-PLA(2) inhibition process and may prove
useful in the design of new anti-inflammatory agents that target PLA(2) secretory
enzymes.
PMID: 12325001 [PubMed - indexed for MEDLINE]
| 8: FEBS Lett. 1999 Apr 1;448(1):62-6. |
Biological
activities of C-terminal 15-residue synthetic fragment of melittin: design
of an analog with improved antibacterial activity.
Subbalakshmi
C, Nagaraj
R, Sitaram
N.
Centre for Cellular and Molecular Biology,
Melittin, the 26-residue predominant toxic peptide from bee venom, exhibits
potent antibacterial activity in addition to its hemolytic activity. The synthetic
peptide of 15 residues corresponding to its C-terminal end (MCF), which encompasses
its most amphiphilic segment, is now being shown to possess antibacterial
activity about 5-7 times less compared to that of melittin. MCF, however,
is 300 times less hemolytic. An analog of MCF, MCFA, in which two cationic
residues have been transpositioned to the N-terminal region from the C-terminal
region, exhibits antibacterial activity comparable to that of melittin, but
is only marginally more hemolytic than MCF. The biophysical properties of
the peptides, like folding and aggregation, correlate well with their biological
properties.
| 9: Yakugaku Zasshi. 1997 May;117(5):253-64. |
[Molecular action
mechanisms and membrane recognition of membrane-acting antimicrobial peptides]
[Article in Japanese]
Matsuzaki
K.
Faculty of Pharmaceutical Sciences,
A number of antimicrobial peptides have been isolated in the animal kingdom,
serving as defensive or offensive weapons. The mechanisms of their action
are considered to be the permeability of bacterial membranes, although the
details are not yet clarified. I have studied the interactions of several
antibiotic peptides with both artificial lipid bilayers and biomembranes to
elucidate the molecular mechanisms of the action and to find out the rationale
for their membrane specificity. Magainin 2 from the Xenopus skin was found
to form a peptide-lipid supramolecular complex pore in the membrane, followed
by peptide internalization, simultaneously dissipating the transmembrane potential
and the lipid asymmetry. This novel mechanism also works for a wasp bee venom,
mastoparan X. Tachyplesin I from Tachypleus and a bee venom, melittin, also
translocate across the membrane by forming a pore. The membrane selectivity
of these peptides is closely related to their affinity for the lipids constituting
the membrane surface. A strategy for developing a potent antibiotic was discussed
based on these results.
· Review
PMID: 9194394 [PubMed - indexed for MEDLINE]
| 10: Biochemistry. 1997 Feb 18;36(7):1826-35. |
Selective
lysis of bacteria but not mammalian cells by diastereomers of melittin: structure-function
study.
Oren
Z, Shai
Y.
Department of Membrane Research and Biophysics, Weizmann Institute of Science,
Studies on lipid-peptide interactions of cytolytic polypeptides tend to emphasize
the importance of the amphipathic alpha-helical structure for their cytolytic
activity. In this study, diasetereomers of the bee venom melittin (
| 11: Res Microbiol. 1997 Feb;148(2):163-75. |
Effect of
natural amphipathic peptides on viability, membrane potential, cell shape
and motility of mollicutes.
Beven
L, Wroblewski
H.
Groupe Membranes et Osmoregulation, UPRES-A CNRS Q6026, Universite de Rennes
1,
The antibiotic activity of ten amphipathic peptides was investigated in six
species of mollicutes belonging to the genera Acholeplasma, Mycoplasma and
Spiroplasma. A. laidlawii was the most sensitive and M. mycoides subsp. mycoides
SC the most resistant. Animal defence peptides (cecropins A and P1, and magainin
2) proved to be less potent than bee-venom mellitin and most of the peptides
produced by bacteria (globomycin, gramicidin S, surfactin and valinomycin)
or fungi (alamethicin). Gramicidin S was by far the most active peptide, with
minimal inhibitory concentrations ranging from 2 to 50 nM. Alamethicin, gramicidin
S, mellitin and surfactin had a cidal effect, whilst cecropins, globomycin,
magainin 2, polymyxin B and valinomycin proved to be static. The peptides
altered the membrane potential of spiroplasma cells with a potency independent
of their linear or cyclic structure. However, globomycin depolarized the plasma
membrane only weakly, whilst polymyxin B, in order to be active, required
prior hyperpolarization of the membrane. The peptides also induced the loss
of cell motility and helicity in spiroplasmas, suggesting that motility and
cell shape in these bacteria are coupled to the transmembrane electrochemical
gradient. Globomycin, an inhibitor of signal-peptidase II, prevented the growth
of spiroplasmas, M. gallisepticum, and M. genitalium, but not that of A. laidlawii
and M. mycoides subsp. mycoides SC, although the latter also synthesized membrane
lipoproteins. Inhibition of spiralin processing by globomycin was demonstrated
in S. citri and S. melliferum, with a more pronounced effect in the second
species.
| 12: J Steroid Biochem Mol Biol. 1997 Jan;60(1-2):51-7. |
Functional dissociation
between glucocorticoid-induced decrease in arachidonic acid release and inhibition
of adrenocorticotropic hormone secretion in AtT-20 corticotrophs.
Pompeo A, Luini A, Buccione R.
Istituto di Richerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud,
Department of Cell Biology and Oncology, Chieti, Italy.
The biochemical basis of the
short-term inhibitory effects of glucocorticoids on corticotropin release
from pituitary corticotrophs is still obscure. A well-characterized effect
of glucocorticoids in several cell types is the inhibition of arachidonic
acid (AA) generation by phospholipase A2 (PLA2). Arachidonic acid and its
metabolites have been implicated in the secretory process from a number of
pituitary cells, such as the corticotrophs. We have thus examined the role
of AA in the anti-secretagogue effects of glucocorticoids in a corticotropin-secreting
clonal corticotroph line (AtT-20 D16/16). Glucocorticoids decreased AA release
induced by melittin, a bee venom protein related to extracellular PLA2. When
a possible role of AA in corticotropin release was studied, the following
results were obtained: (a) all corticotropin secretagogues tested, including
corticotropin-releasing factor (CRF), did not alter AA generation; (b) calcium
and guanine nucleotides, which stimulate corticotropin release in permeabilized
cells, inhibited the release of AA under the same conditions; (c) administration
of melittin or of exogenous AA had no effect on basal and CRF-stimulated corticotropin
release; (d) administration of large amounts of exogenous AA was unable to
restore the ability to secrete corticotropin under suppression by glucocorticoids.
Altogether, the data suggest that whereas glucocorticoids can inhibit both
AA generation and corticotropin release, these two effects appear to be causally
unrelated.
PMID: 9182858 [PubMed - indexed for MEDLINE]
| 13: Curr Microbiol. 1996 Nov;33(5):317-22. |
Inhibition
of spiralin processing by the lipopeptide antibiotic globomycin.
Beven L, Le Henaff M,
Fontenelle C,
Wroblewski H.
Equipe "Membranes et Osmoregulation," CNRS URA No. 256, Universite
de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France.
The cyclic lipopeptide globomycin,
a specific inhibitor of signal-peptidase II (Lsp A), proved toxic for the
mollicute Spiroplasma melliferum with a minimal inhibitory concentration (MIC)
in the range 6.25-12.5 microM, about one order of magnitude higher (that is,
less efficient) than bee-venom mellitin. SDS-PAGE analysis of cell proteins
followed by immunolabeling ("Western blotting") and by crossed immunoelectrophoresis
demonstrated that the cleavage of the prespiralin leader peptide was prevented
by globomycin. Cell fractionation experiments showed that prespiralin was
membrane bound and did not accumulate in the cytoplasm or in the culture medium.
Furthermore, the use of the potential-sensitive fluorescent dye 3,3'-dipropyl-2,2'-thiadicarbocyanine
iodide (diS-C3-[5]) revealed that, in contrast to valinomycin and mellitin,
globomycin up to 30 microM has no effect on the electrical transmembrane potential
of S. melliferum. This indicates that the toxicity of globomycin for spiroplasma
cells is mainly if not exclusively owing to the inhibition of spiralin processing.
Added to previously published data, these results suggest that spiralin and
probably other lipoproteins of mollicutes are acylated and membrane targeted
by a mechanism involving notably the processing of the prelipoprotein precursor
by a type II, globomycin-sensitive signal peptidase.
PMID: 8875913 [PubMed - indexed for MEDLINE]
| 14: Singapore Med J. 1996 Aug;37(4):389-91. |
Case reports and
mini review of bee stings of the cornea.
Chuah
G, Law
E, Chan
WK, Ang
CL.
Bee stings of the eye are not uncommon. Quite a few clinical case reports
have documented the various ocular reactions to the venom of the bee stings,
which may range from mild conjunctivitis to sudden loss of vision. This report
presents 2 patients who suffered bee stings to the cornea and their different
outcomes. The properties of bee venom as well as the treatment of various
possible complications are also discussed.
· Review
PMID: 8993139 [PubMed - indexed for MEDLINE]
| 15: Biochim Biophys Acta. 1994 Jul 21;1222(3):471-6. |
Melittin inhibits
epidermal growth factor-induced protein tyrosine phosphorylation: comparison
with phorbol myristate acetate and calcium ionophore A23187.
Errasfa
M, Stern
A.
Department of Pharmacology,
In HER14 cells, epidermal growth factor (EGF) induces tyrosine phosphorylation
of several proteins, including its own receptor. The bee venom peptide, melittin,
impaired EGF-dependent protein tyrosine phosphorylation in a calcium-dependent
manner. The melittin effect was similarly reproduced by calcium ionophore
A23187. The effect of melittin and calcium ionophore A23187 on EGF-dependent
protein tyrosine phosphorylation was abolished by treatment of cells with
the calcium chelator EGTA. Phorbol-myristate acetate (PMA) inhibited EGF-dependent
protein tyrosine phosphorylation, and when compared to melittin or calcium
ionophore A23187, only PMA potentiated the EGF-induced tyrosine phosphorylation
of two proteins immunologically related to mitogen activated protein (MAP)
kinases of 40 kDa and 44 kDa molecular mass. Unlike PMA, the effect of melittin
and calcium ionophore A23187 on inhibition of EGF-dependent protein tyrosine
phosphorylation was lost neither in protein kinase C-depleted cells nor in
cells treated with the protein tyrosine phosphatase inhibitors NaF and Na3VO4.
Melittin inhibited high affinity binding of EGF to its receptor in intact
cells, but this effect was not prevented by EGTA. It is concluded that melittin
and calcium ionophore A23187 differ from PMA in their inhibition of EGF-dependent
protein tyrosine phosphorylation in vivo, by acting via a Ca(2+)-dependent
pathway, that is independent of protein kinase C, protein tyrosine phosphatase
activity and high affinity binding of EGF to its receptor.
| 16: J Med Chem. 1993 Jun 25;36(13):1866-79. |
Molecular model
of the interaction of bee venom phospholipase A2 with manoalide.
Ortiz AR, Pisabarro MT,
Gago F.
Departamento de Fisiologia y Farmacologia, Universidad de Alcala de Henares,
Madrid, Spain.
A molecular model of the interaction
between manoalide (MLD) and bee venom phospholipase A2 (bv-PLA2) has been
derived making use of a combination of computational methods. MLD was built
in its open form and simulated by using molecular dynamics techniques. It
is shown that the polar part of the molecule, which is thought to be the reactive
region, is endowed with considerable conformational flexibility whereas the
apolar region is rather rigid. The proposed active conformation of MLD and
the main putative binding site for MLD on this enzyme were identified by matching
potential energy GRID maps for both ligand and receptor with the chemical
structure of the respective counterpart. The binding site is found in the
C-terminal region of bv-PLA2, forming part of the proposed interfacial surface
for binding to aggregated substrates, and comprises two distinct regions:
(i) a hydrophobic cavity delimited by the C-terminal beta-sheet and the antiparallel
beta-sheet, which interacts with the apolar zone of MLD, and (ii) a cationic
site made up of residues Arg-58 and Lys-94, which interacts with the polar
zone. Molecular dynamics and molecular orbital calculations indicate that
the most likely initial reaction between MLD and bv-PLA2 is formation of a
Schiff base between Lys-94 and the aldehyde generated upon opening of MLD's
gamma-lactone ring, supporting recent model reaction studies. The inhibition
seems to be a consequence of the occupation by MLD of a site overlapping a
phosphocholine binding site in bv-PLA2 presumably involved in the interface
desolvation process. The present model represents a starting point for further
structural studies on the mechanism of phospholipases A2 inactivation by MLD
and MLD-like compounds.
PMID: 8515424 [PubMed - indexed for MEDLINE]
| 17: Oncogene. 1993 Apr;8(4):939-47. |
Melittin-induced
hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed
cells.
Sharma
SV.
Department of Microbiology and Immunology,
The activated ras oncogene is a key mediator of cellular transformation and
is present in a wide variety of primary human neoplasms. The biochemical role
of the ras oncogene in cellular transformation is at present unclear, and
hence approaches to control its activities in transformed cells have met with
limited success. Previous studies have demonstrated the ability of melittin,
a 26 amino acid amphipathic peptide from bee venom, to specifically counterselect
for cells in culture that express high levels of the ras oncogene product.
The biochemical basis for this counterselection is currently unknown. This
study demonstrates the ability of melittin to hyperactivate phospholipase
A2 (PLA2) in ras-transformed cells by the mediation of enhanced influx of
calcium ions (Ca2+). This hyperactivation of PLA2 and Ca2+ mobilization in
ras-transformed cells by melittin is mimicked by the calcium ionophore, A23187.
Both melittin- and A23187-mediated PLA2 hyperactivation require Ca2+. However,
the action of melittin is strongly dependent on extracellular Ca2+, whereas
that of A23187 is not. Melittin-induced Ca2+ influx and PLA2 hyperactivation
is inhibited by manganese ions (Mn2+). These studies reveal a close correlation
between the extent of PLA2 hyperactivation and Ca2+ mobilization, suggesting
a causal relationship.
| 18: Agents Actions. 1991 Sep;34(1-2):70-2. |
AGN
De Vries
GW, Lee
G, Amdahl
L, Wenzel
M, Garst
M, Wheeler
LA.
Department of Biological Sciences, Allergan, Inc.,
AGN 190383 is a 5-hydroxy-2(5H)-furanone ring analog of the marine natural
product manoalide. When applied topically, AGN 190383 inhibits phorbol ester
induced mouse ear edema. It is a potent inhibitor of bee venom phospholipase
A2 and blocks the release of arachidonic acid from calcium ionophore A23187
stimulated human neutrophils. AGN 190383 also inhibits both hormone-operated
and depolarization-dependent calcium mobilization in GH3 cells, as well as
fMLP stimulated increases in free cytosolic calcium in human PMNs. Furthermore,
it is also able to block the release of the neutral protease elastase from
stimulated neutrophils. The effects of AGN 190383 on arachidonic acid metabolism
and leukocyte function may account, in part, for its anti-inflammatory activity
in vivo.
| 19: Chem Phys Lipids. 1991 Mar;57(2-3):327-40. |
Polymorphic phospholipid
phase transitions as tools to understand peptide-lipid interactions.
Tournois
H, de Kruijff
B.
aATO Agrotechnology, Wageningen, The Netherlands.
The effect of peptides on bilayer----non-bilayer phase transitions can be
used as a tool to investigate the molecular aspects of peptide-lipid interactions.
In this contribution the action on membranes of the peptide antibiotic gramicidin
A and the bee venom component melittin are compared. Although the known structures
and locations of these peptides upon membrane binding are very different,
their actions on membranes show striking parallels. A general model is proposed
that explains the seemingly complex peptide-lipid interactions by making use
of simple concepts.
Publication Types:
· Review
PMID: 1711420 [PubMed - indexed for MEDLINE]
| 20: J Biol Chem. 1991 Feb 15;266(5):2753-8. |
Membrane
interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B,
and cardiotoxin. Differential inhibition of protein kinase C, Ca2+/calmodulin-dependent
protein kinase II and synaptosomal membrane Na,K-ATPase, and Na+ pump and
differentiation of HL60 cells.
Raynor
RL, Zheng
B, Kuo
JF.
Department of Pharmacology,
Interactions of certain naturally occurring, amphiphilic polypeptides with
membranes were investigated. Mastoparan (wasp venom toxin), melittin (bee
venom toxin), cardiotoxin (cobra venom toxin), and polymyxin B (antibacterial
antibiotic) inhibited protein kinase C stimulated by phosphatidylserine bilayer
or arachidonate monomer and blocked binding of [3H] phorbol 12,13-dibutyrate
to protein kinase C in the presence of phosphatidylserine bilayer, with IC50
values (concentrations causing 50% inhibition) of 1-8 microM. Mastoparan and
polymyxin B were much less inhibitory (IC50, 10-20 microM), whereas melittin
and cardiotoxin were similarly inhibitory (IC50, 1-4 microM), when protein
kinase C was activated instead by synaptosomal membrane. Kinetic analysis
indicate that mastoparan inhibited protein kinase C, assayed using phosphatidylserine
or synaptosomal membrane as the phospholipid cofactor, competitively with
the phospholipid cofactor, in a mixed manner with CaCl2 or diacylglycerol,
noncompetitively with histone, and uncompetitively with ATP, with apparent
Ki values of 1.6-18.7 microM. Inhibition of Na,K-ATPase in the membrane by
these polypeptides had relative potencies different from those for their inhibition
of protein kinase C activated by the same membrane preparation; mastoparan
and melittin inhibited the two activities with comparable potencies, but polymyxin
B and cardiotoxin were far less effective in inhibiting Na,K-ATPase. The same
relative inhibitory potencies of the polypeptides (melittin greater than mastoparan
greater than polymyxin B) for inhibition of Na,K-ATPase were also noted for
their inhibition of Ca2+/calmodulin-dependent protein kinase II, 86Rb uptake
(Na+ pump) by HL60 cells and the phorbol ester-induced differentiation of
the leukemia cells. These findings were consistent with discrete interactions
of the polypeptides with functionally distinct sites on the membrane, leading
to differential inhibition of biological activities associated with the membrane.
Actions of certain polypeptides appeared to be more specific compared to those
of lipid second messengers such as lyso-phosphatidylcholine and sphingosine,
and the antineoplastic ether lipid analogs such as 1-O-octadecyl-2-methyl-rac-glycero-3-ophosphocholine.
| 21: Infect Immun. 1990 Aug;58(8):2678-82. |
Effect of
staphylococcal delta-toxin and bee venom peptide melittin on leukotriene induction
and metabolism of human polymorphonuclear granulocytes.
Raulf
M, Alouf
JE, Konig
W.
Lehrstuhl fur Medizinische Mikrobiologie und Immunologie, Ruhr-Universitat
Bochum, Federal Republic of Germany.
The abilities of delta-toxin from Staphylococcus aureus and melittin to induce
and modulate the generation of leukotriene from human polymorphonuclear granulocytes
(PMNs) were studied. Stimulation of PMNs with melittin (10 micrograms) induced
leukotriene formation, whereas stimulation with delta-toxin did not. Preincubation
of the PMNs with delta-toxin modulated the subsequent generation of leukotriene
from PMNs induced by Ca ionophore A23187 or opsonized zymosan. The generation
of leukotriene B4 (LTB4), induced by the Ca ionophore A23187, was increased
when the PMNs were preincubated with delta-toxin for 5 min. When opsonized
zymosan was used as a secondary stimulus to activate the delta-toxin-pretreated
PMNs, LTB4 generation decreased. In contrast, melittin showed no significant
modulatory effect on the generation of leukotriene from PMNs. In addition,
preincubation of PMNs with delta-toxin inhibited the conversion of LTB4 to
omega-oxidation products. Our data suggest that peptides with similar structures,
e.g., delta-toxin and melittin, induce and modify leukotriene generation in
different manners.
PMID: 2164512 [PubMed - indexed for MEDLINE]
| 22: FEBS Lett. 1989 Dec 18;259(1):103-6. |
Antibacterial
and antimalarial properties of peptides that are cecropin-melittin hybrids.
Boman
HG, Wade
D, Boman
IA, Wahlin
B, Merrifield
RB.
Department of Microbiology,
Solid phase synthesis was used to produce 5 hybrid peptides containing sequences
from the antibacterial peptide, cecropin A, and from the bee venom toxin,
melittin. Four of these chimeric peptides showed good antibacterial activity
against representative Gram-negative and Gram-positive bacterial species.
The best hybrid, cecropin A(1-13)-melittin(1-13) was 100-fold more active
than cecropin A against Staphylococcus aureus. It was also a 10-fold better
antimalarial agent than cecropin B or magainin 2. Sheep red cells were lysed
by melittin at low concentrations, but not by the hybrid molecules, even at
50 times higher concentrations.
| 23: Zentralbl Bakteriol. 1989 Oct;271(4):521-31. |
Inhibition of in
vitro and in vivo mast cell degranulation by Taenia crassiceps metacestodes
in vitro incubation products.
Seifert
B, Geyer
E.
Fachbereich Biologie, Philipps-Universitat,
In vitro released products of T. crassiceps metacestodes (TcIP) harvested
from the peritoneal cavity of NMRI mice were tested for inhibitory effects
on the in vitro degranulation of peritoneal mast cells (MCs) of normal mice
(NMRI) and rats (Wistar) and on the in vivo degranulation of rat (Wistar)
skin MCs (PCA-assay). In vitro degranulation was elicited chemically (compound
48/80, polymyxin B or the bee venom peptide, mellitin). In vivo degranulation
was triggered immunologically (anaphylactic systems ovalbumin/anti-ovalbumin
or Fasciola hepatica crude fluke extract antigen/serum of fluke-infected rats
(Wistar]. In vitro degranulation of murine peritoneal MCs or the in vitro
histamine release of rat peritoneal MCs normally induced chemically was significantly
inhibited when the MCs were preincubated with the TcIP or with serum of T.
crassiceps-infected NMRI mice from day 35 post infection and thereafter. In
vitro degranulation of peritoneal MCs of infected mice was strongly inhibited
beginning on day 10 after infection. Also in vivo degranulation of the IgE-sensitized
rat skin MCs was significantly reduced by intradermal injection of the TcIP
before (6, 3 and 1 h) antigen challenge and by preinjection (1 h) of serum
from infected mice (day 80 p.i.)-The inhibitory effect was also demonstrated
after immunoadsorption of mouse serum proteins naturally contaminating the
TcIP. Heating (100 degrees C/15 min), even in the presence of
| 24: J Pharm Pharmacol. 1989 Jul;41(7):450-8. |
Inhibition of Na+,K+-ATPase
activity by phospholipase A2 and several lysophospholipids: possible role
of phospholipase A2 in noradrenaline release from cerebral cortical synaptosomes.
Nishikawa
T, Tomori
Y, Yamashita
S, Shimizu
S.
Department of Pharmacology,
p-Bromophenacyl bromide (PBPB), quinacrine and indomethacin, which inhibit
phospholipase A2 (PLA2; EC 3.1.1.4) activity in several tissues, caused a
dose-dependent inhibition of prelabelled [3H]noradrenaline ([3H]NA) release
evoked by high concentrations of K+ from rat cerebral cortical synaptosomes.
Release of prelabelled [3H]NA was caused by natural lysophosphatidic acid
(LPA; 10(-6)-10(-5) g mL-1) and lysophosphatidylcholine (LPC; 10(-6)-10(-5)
g mL-1) and synthetic LPA (6 x 10(-6), 2 x 10(-5) M) and LPC (6 x 10(-6),
2 x 10(-5) M), but not by natural lysophosphatidylserine (LPS; 10(-5) g mL-1),
lysophosphatidylethanolamine (LPE; 10(-5) g mL-1) and lysophosphatidylinositol
(LPI; 10(-5) g mL-1). The release evoked by natural LPA and LPC could be inhibited
only marginally by PBPB and quinacrine. Phosphatidic acid (PA)-specific and
phosphatidylcholine (PC)-specific PLA2 activities from rat cerebral cortical
synaptosomes were stimulated in incubation medium containing high concentrations
of K+ or calcium ionophore A23187. Low concentrations of PLA2 (10(-6)-10(-8)
g mL-1, from bee venom) inhibited the synaptic membrane Na+,K+-ATPase activity
in incubation media with intracellular levels of free Ca2+. Several lysophospholipids
(LPLs), metabolites of the PLA2 type, also inhibited the synaptic membrane
Na+,K+-ATPase activity in a dose-dependent manner. The minimum effective concentrations
of natural LPA, LPC, LPS, LPI and LPE were 10(-6), 4.7 x 10(-6), 10(-5), 4.7
x 10(-5) and 4.7 x 10(-5) g mL-1, respectively.(ABSTRACT TRUNCATED AT 250
WORDS)
PMID: 2570849 [PubMed - indexed for MEDLINE]
| 25: Biochem Pharmacol. 1988 Oct 1;37(19):3639-46. |
Inactivation of
phospholipase A2 by manoalide. Localization of the manoalide binding site
on bee venom phospholipase A2.
Glaser
KB, Vedvick
TS