Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?
Identifieur interne : 002D15 ( Main/Exploration ); précédent : 002D14; suivant : 002D16Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?
Auteurs : M. Malisauskas [Suède] ; A. Darinskas ; V V Zamotin ; A. Gharibyan ; I A Kostanyan ; L A Morozova-RocheSource :
- Biochemistry. Biokhimiia [ 0006-2979 ] ; 2006.
Descripteurs français
- KwdFr :
- Amyloïde (), Amyloïde (métabolisme), Amyloïde (toxicité), Amyloïdose (anatomopathologie), Amyloïdose (métabolisme), Amyloïdose (étiologie), Animaux, Benzothiazoles, Cellules cultivées, Cinétique, Concentration en ions d'hydrogène, Dimérisation, Equus caballus, Femelle, Humains, Lignée cellulaire tumorale, Lysozyme (), Lysozyme (métabolisme), Lysozyme (toxicité), Microscopie à force atomique (), Modèles moléculaires, Peptides bêta-amyloïdes (), Peptides bêta-amyloïdes (métabolisme), Rouge Congo (), Souris, Souris de lignée BALB C, Structure secondaire des protéines, Structures macromoléculaires (), Structures macromoléculaires (métabolisme), Survie cellulaire (), Thiazoles ().
- MESH :
- anatomopathologie : Amyloïdose.
- métabolisme : Amyloïde, Amyloïdose, Lysozyme, Peptides bêta-amyloïdes, Structures macromoléculaires.
- toxicité : Amyloïde, Lysozyme.
- étiologie : Amyloïdose.
- Amyloïde, Animaux, Benzothiazoles, Cellules cultivées, Cinétique, Concentration en ions d'hydrogène, Dimérisation, Equus caballus, Femelle, Humains, Lignée cellulaire tumorale, Lysozyme, Microscopie à force atomique, Modèles moléculaires, Peptides bêta-amyloïdes, Rouge Congo, Souris, Souris de lignée BALB C, Structure secondaire des protéines, Structures macromoléculaires, Survie cellulaire, Thiazoles.
English descriptors
- KwdEn :
- Amyloid (chemistry), Amyloid (metabolism), Amyloid (toxicity), Amyloid beta-Peptides (chemistry), Amyloid beta-Peptides (metabolism), Amyloidosis (etiology), Amyloidosis (metabolism), Amyloidosis (pathology), Animals, Benzothiazoles, Cell Line, Tumor, Cell Survival (drug effects), Cells, Cultured, Congo Red (chemistry), Dimerization, Female, Horses, Humans, Hydrogen-Ion Concentration, Kinetics, Macromolecular Substances (chemistry), Macromolecular Substances (metabolism), Mice, Mice, Inbred BALB C, Microscopy, Atomic Force (methods), Models, Molecular, Muramidase (chemistry), Muramidase (metabolism), Muramidase (toxicity), Protein Structure, Secondary, Thiazoles (chemistry).
- MESH :
- chemical , chemistry : Amyloid, Amyloid beta-Peptides, Congo Red, Macromolecular Substances, Muramidase, Thiazoles.
- chemical , metabolism : Amyloid, Amyloid beta-Peptides, Macromolecular Substances, Muramidase.
- chemical , toxicity : Amyloid, Muramidase.
- drug effects : Cell Survival.
- etiology : Amyloidosis.
- metabolism : Amyloidosis.
- methods : Microscopy, Atomic Force.
- pathology : Amyloidosis.
- Animals, Benzothiazoles, Cell Line, Tumor, Cells, Cultured, Dimerization, Female, Horses, Humans, Hydrogen-Ion Concentration, Kinetics, Mice, Mice, Inbred BALB C, Models, Molecular, Protein Structure, Secondary.
Abstract
In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.5 and 57 degrees C. These structures bind the amyloid-specific dyes thioflavin T and Congo Red, and their morphology and size were analyzed by atomic force microscopy. Monomeric lysozyme and its fibrils did not affect the viability of three cell types used in our experiments including primary murine neurons and fibroblasts, as well as neuroblastoma cell line IMR-32. However, soluble amyloid oligomers of lysozyme caused death of all these cell types, as estimated by flow-cytometry counting dead cells stained with ethidium bromide. The primary cell cultures appeared to be more sensitive to amyloid than neuroblastoma cell line IMR-32. Amyloid cytotoxicity depends on the size of oligomeric particles: samples containing 20-mers formed at pH 4.5 were more toxic than tetramers and octamers present in the solution at pH 2.0. Soluble amyloid oligomers can self-assemble into doughnut-like structures; however, no correlation was observed between the amount of the doughnut-like structures in the sample and its cytotoxicity. The fact that the intermediate oligomers of such an abundant protein as lysozyme display cytotoxicity confirms a hypothesis that cytotoxicity is a common feature of protein amyloid. Inhibition of intermediate oligomer formation is crucial in preventing amyloid pathogeneses.
DOI: 10.1134/s0006297906050063
PubMed: 16732728
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002253
- to stream PubMed, to step Curation: 002253
- to stream PubMed, to step Checkpoint: 002117
- to stream Ncbi, to step Merge: 000436
- to stream Ncbi, to step Curation: 000436
- to stream Ncbi, to step Checkpoint: 000436
- to stream Main, to step Merge: 002D42
- to stream Main, to step Curation: 002D15
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?</title><author><name sortKey="Malisauskas, M" sort="Malisauskas, M" uniqKey="Malisauskas M" first="M" last="Malisauskas">M. Malisauskas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Biochemistry and Biophysics, Umea University, Umea 90187, Sweden. mantas.malisauskas@medchem.umu.se</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Biochemistry and Biophysics, Umea University, Umea 90187</wicri:regionArea><wicri:noRegion>Umea 90187</wicri:noRegion></affiliation></author><author><name sortKey="Darinskas, A" sort="Darinskas, A" uniqKey="Darinskas A" first="A" last="Darinskas">A. Darinskas</name></author><author><name sortKey="Zamotin, V V" sort="Zamotin, V V" uniqKey="Zamotin V" first="V V" last="Zamotin">V V Zamotin</name></author><author><name sortKey="Gharibyan, A" sort="Gharibyan, A" uniqKey="Gharibyan A" first="A" last="Gharibyan">A. Gharibyan</name></author><author><name sortKey="Kostanyan, I A" sort="Kostanyan, I A" uniqKey="Kostanyan I" first="I A" last="Kostanyan">I A Kostanyan</name></author><author><name sortKey="Morozova Roche, L A" sort="Morozova Roche, L A" uniqKey="Morozova Roche L" first="L A" last="Morozova-Roche">L A Morozova-Roche</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16732728</idno><idno type="pmid">16732728</idno><idno type="doi">10.1134/s0006297906050063</idno><idno type="wicri:Area/PubMed/Corpus">002253</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002253</idno><idno type="wicri:Area/PubMed/Curation">002253</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002253</idno><idno type="wicri:Area/PubMed/Checkpoint">002117</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002117</idno><idno type="wicri:Area/Ncbi/Merge">000436</idno><idno type="wicri:Area/Ncbi/Curation">000436</idno><idno type="wicri:Area/Ncbi/Checkpoint">000436</idno><idno type="wicri:doubleKey">0006-2979:2006:Malisauskas M:intermediate:amyloid:oligomers</idno><idno type="wicri:Area/Main/Merge">002D42</idno><idno type="wicri:Area/Main/Curation">002D15</idno><idno type="wicri:Area/Main/Exploration">002D15</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?</title><author><name sortKey="Malisauskas, M" sort="Malisauskas, M" uniqKey="Malisauskas M" first="M" last="Malisauskas">M. Malisauskas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Biochemistry and Biophysics, Umea University, Umea 90187, Sweden. mantas.malisauskas@medchem.umu.se</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Biochemistry and Biophysics, Umea University, Umea 90187</wicri:regionArea><wicri:noRegion>Umea 90187</wicri:noRegion></affiliation></author><author><name sortKey="Darinskas, A" sort="Darinskas, A" uniqKey="Darinskas A" first="A" last="Darinskas">A. Darinskas</name></author><author><name sortKey="Zamotin, V V" sort="Zamotin, V V" uniqKey="Zamotin V" first="V V" last="Zamotin">V V Zamotin</name></author><author><name sortKey="Gharibyan, A" sort="Gharibyan, A" uniqKey="Gharibyan A" first="A" last="Gharibyan">A. Gharibyan</name></author><author><name sortKey="Kostanyan, I A" sort="Kostanyan, I A" uniqKey="Kostanyan I" first="I A" last="Kostanyan">I A Kostanyan</name></author><author><name sortKey="Morozova Roche, L A" sort="Morozova Roche, L A" uniqKey="Morozova Roche L" first="L A" last="Morozova-Roche">L A Morozova-Roche</name></author></analytic><series><title level="j">Biochemistry. Biokhimiia</title><idno type="ISSN">0006-2979</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amyloid (chemistry)</term><term>Amyloid (metabolism)</term><term>Amyloid (toxicity)</term><term>Amyloid beta-Peptides (chemistry)</term><term>Amyloid beta-Peptides (metabolism)</term><term>Amyloidosis (etiology)</term><term>Amyloidosis (metabolism)</term><term>Amyloidosis (pathology)</term><term>Animals</term><term>Benzothiazoles</term><term>Cell Line, Tumor</term><term>Cell Survival (drug effects)</term><term>Cells, Cultured</term><term>Congo Red (chemistry)</term><term>Dimerization</term><term>Female</term><term>Horses</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Kinetics</term><term>Macromolecular Substances (chemistry)</term><term>Macromolecular Substances (metabolism)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Microscopy, Atomic Force (methods)</term><term>Models, Molecular</term><term>Muramidase (chemistry)</term><term>Muramidase (metabolism)</term><term>Muramidase (toxicity)</term><term>Protein Structure, Secondary</term><term>Thiazoles (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amyloïde ()</term><term>Amyloïde (métabolisme)</term><term>Amyloïde (toxicité)</term><term>Amyloïdose (anatomopathologie)</term><term>Amyloïdose (métabolisme)</term><term>Amyloïdose (étiologie)</term><term>Animaux</term><term>Benzothiazoles</term><term>Cellules cultivées</term><term>Cinétique</term><term>Concentration en ions d'hydrogène</term><term>Dimérisation</term><term>Equus caballus</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Lysozyme ()</term><term>Lysozyme (métabolisme)</term><term>Lysozyme (toxicité)</term><term>Microscopie à force atomique ()</term><term>Modèles moléculaires</term><term>Peptides bêta-amyloïdes ()</term><term>Peptides bêta-amyloïdes (métabolisme)</term><term>Rouge Congo ()</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Structure secondaire des protéines</term><term>Structures macromoléculaires ()</term><term>Structures macromoléculaires (métabolisme)</term><term>Survie cellulaire ()</term><term>Thiazoles ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amyloid</term><term>Amyloid beta-Peptides</term><term>Congo Red</term><term>Macromolecular Substances</term><term>Muramidase</term><term>Thiazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amyloid</term><term>Amyloid beta-Peptides</term><term>Macromolecular Substances</term><term>Muramidase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Amyloid</term><term>Muramidase</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Amyloïdose</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Amyloidosis</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Amyloidosis</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Microscopy, Atomic Force</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Amyloïde</term><term>Amyloïdose</term><term>Lysozyme</term><term>Peptides bêta-amyloïdes</term><term>Structures macromoléculaires</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Amyloidosis</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Amyloïde</term><term>Lysozyme</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Amyloïdose</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Benzothiazoles</term><term>Cell Line, Tumor</term><term>Cells, Cultured</term><term>Dimerization</term><term>Female</term><term>Horses</term><term>Humans</term><term>Hydrogen-Ion Concentration</term><term>Kinetics</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Models, Molecular</term><term>Protein Structure, Secondary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amyloïde</term><term>Animaux</term><term>Benzothiazoles</term><term>Cellules cultivées</term><term>Cinétique</term><term>Concentration en ions d'hydrogène</term><term>Dimérisation</term><term>Equus caballus</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Lysozyme</term><term>Microscopie à force atomique</term><term>Modèles moléculaires</term><term>Peptides bêta-amyloïdes</term><term>Rouge Congo</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Structure secondaire des protéines</term><term>Structures macromoléculaires</term><term>Survie cellulaire</term><term>Thiazoles</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.5 and 57 degrees C. These structures bind the amyloid-specific dyes thioflavin T and Congo Red, and their morphology and size were analyzed by atomic force microscopy. Monomeric lysozyme and its fibrils did not affect the viability of three cell types used in our experiments including primary murine neurons and fibroblasts, as well as neuroblastoma cell line IMR-32. However, soluble amyloid oligomers of lysozyme caused death of all these cell types, as estimated by flow-cytometry counting dead cells stained with ethidium bromide. The primary cell cultures appeared to be more sensitive to amyloid than neuroblastoma cell line IMR-32. Amyloid cytotoxicity depends on the size of oligomeric particles: samples containing 20-mers formed at pH 4.5 were more toxic than tetramers and octamers present in the solution at pH 2.0. Soluble amyloid oligomers can self-assemble into doughnut-like structures; however, no correlation was observed between the amount of the doughnut-like structures in the sample and its cytotoxicity. The fact that the intermediate oligomers of such an abundant protein as lysozyme display cytotoxicity confirms a hypothesis that cytotoxicity is a common feature of protein amyloid. Inhibition of intermediate oligomer formation is crucial in preventing amyloid pathogeneses.</div></front></TEI><affiliations><list><country><li>Suède</li></country></list><tree><noCountry><name sortKey="Darinskas, A" sort="Darinskas, A" uniqKey="Darinskas A" first="A" last="Darinskas">A. Darinskas</name><name sortKey="Gharibyan, A" sort="Gharibyan, A" uniqKey="Gharibyan A" first="A" last="Gharibyan">A. Gharibyan</name><name sortKey="Kostanyan, I A" sort="Kostanyan, I A" uniqKey="Kostanyan I" first="I A" last="Kostanyan">I A Kostanyan</name><name sortKey="Morozova Roche, L A" sort="Morozova Roche, L A" uniqKey="Morozova Roche L" first="L A" last="Morozova-Roche">L A Morozova-Roche</name><name sortKey="Zamotin, V V" sort="Zamotin, V V" uniqKey="Zamotin V" first="V V" last="Zamotin">V V Zamotin</name></noCountry><country name="Suède"><noRegion><name sortKey="Malisauskas, M" sort="Malisauskas, M" uniqKey="Malisauskas M" first="M" last="Malisauskas">M. Malisauskas</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002D15 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002D15 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:16732728
|texte= Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:16732728" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |