Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin.
Identifieur interne : 001172 ( Main/Exploration ); précédent : 001171; suivant : 001173Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin.
Auteurs : Maja Misirkic [Serbie] ; Kristina Janjetovic ; Ljubica Vucicevic ; Gordana Tovilovic ; Biljana Ristic ; Urosh Vilimanovich ; Ljubica Harhaji-Trajkovic ; Mirjana Sumarac-Dumanovic ; Dragan Micic ; Vladimir Bumbasirevic ; Vladimir TrajkovicSource :
- Pharmacological research [ 1096-1186 ] ; 2012.
Descripteurs français
- KwdFr :
- AMP-Activated Protein Kinases (antagonistes et inhibiteurs), AMP-Activated Protein Kinases (génétique), AMP-Activated Protein Kinases (métabolisme), Animaux (MeSH), Apoptose (effets des médicaments et des substances chimiques), Autophagie (effets des médicaments et des substances chimiques), Bécline-1 (MeSH), Gliome (anatomopathologie), Gliome (enzymologie), Gliome (génétique), Humains (MeSH), Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (pharmacologie), Inhibiteurs de protéines kinases (pharmacologie), Interférence par ARN (MeSH), Lignée cellulaire tumorale (MeSH), Protocoles de polychimiothérapie antinéoplasique (pharmacologie), Protéines associées aux microtubules (métabolisme), Protéines membranaires (métabolisme), Protéines proto-oncogènes c-akt (métabolisme), Protéines régulatrices de l'apoptose (métabolisme), Rats (MeSH), Relation dose-effet des médicaments (MeSH), Simvastatine (pharmacologie), Souris (MeSH), Survie cellulaire (effets des médicaments et des substances chimiques), Sérine-thréonine kinases TOR (métabolisme), Transduction du signal (effets des médicaments et des substances chimiques), Transfection (MeSH), Tumeurs du cerveau (anatomopathologie), Tumeurs du cerveau (enzymologie), Tumeurs du cerveau (génétique).
- MESH :
- anatomopathologie : Gliome, Tumeurs du cerveau.
- antagonistes et inhibiteurs : AMP-Activated Protein Kinases.
- effets des médicaments et des substances chimiques : Apoptose, Autophagie, Survie cellulaire, Transduction du signal.
- enzymologie : Gliome, Tumeurs du cerveau.
- génétique : AMP-Activated Protein Kinases, Gliome, Tumeurs du cerveau.
- métabolisme : AMP-Activated Protein Kinases, Protéines associées aux microtubules, Protéines membranaires, Protéines proto-oncogènes c-akt, Protéines régulatrices de l'apoptose, Sérine-thréonine kinases TOR.
- pharmacologie : Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase, Inhibiteurs de protéines kinases, Protocoles de polychimiothérapie antinéoplasique, Simvastatine.
- Animaux, Bécline-1, Humains, Interférence par ARN, Lignée cellulaire tumorale, Rats, Relation dose-effet des médicaments, Souris, Transfection.
English descriptors
- KwdEn :
- AMP-Activated Protein Kinases (antagonists & inhibitors), AMP-Activated Protein Kinases (genetics), AMP-Activated Protein Kinases (metabolism), Animals (MeSH), Antineoplastic Combined Chemotherapy Protocols (pharmacology), Apoptosis (drug effects), Apoptosis Regulatory Proteins (metabolism), Autophagy (drug effects), Beclin-1 (MeSH), Brain Neoplasms (enzymology), Brain Neoplasms (genetics), Brain Neoplasms (pathology), Cell Line, Tumor (MeSH), Cell Survival (drug effects), Dose-Response Relationship, Drug (MeSH), Glioma (enzymology), Glioma (genetics), Glioma (pathology), Humans (MeSH), Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology), Membrane Proteins (metabolism), Mice (MeSH), Microtubule-Associated Proteins (metabolism), Protein Kinase Inhibitors (pharmacology), Proto-Oncogene Proteins c-akt (metabolism), RNA Interference (MeSH), Rats (MeSH), Signal Transduction (drug effects), Simvastatin (pharmacology), TOR Serine-Threonine Kinases (metabolism), Transfection (MeSH).
- MESH :
- chemical , antagonists & inhibitors : AMP-Activated Protein Kinases.
- chemical , genetics : AMP-Activated Protein Kinases.
- chemical , metabolism : AMP-Activated Protein Kinases, Apoptosis Regulatory Proteins, Membrane Proteins, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases.
- drug effects : Apoptosis, Autophagy, Cell Survival, Signal Transduction.
- enzymology : Brain Neoplasms, Glioma.
- genetics : Brain Neoplasms, Glioma.
- pathology : Brain Neoplasms, Glioma.
- pharmacology : Antineoplastic Combined Chemotherapy Protocols, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Protein Kinase Inhibitors, Simvastatin.
- Animals, Beclin-1, Cell Line, Tumor, Dose-Response Relationship, Drug, Humans, Mice, RNA Interference, Rats, Transfection.
Abstract
The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.
DOI: 10.1016/j.phrs.2011.08.003
PubMed: 21871960
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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first="Ljubica" last="Vucicevic">Ljubica Vucicevic</name></author><author><name sortKey="Tovilovic, Gordana" sort="Tovilovic, Gordana" uniqKey="Tovilovic G" first="Gordana" last="Tovilovic">Gordana Tovilovic</name></author><author><name sortKey="Ristic, Biljana" sort="Ristic, Biljana" uniqKey="Ristic B" first="Biljana" last="Ristic">Biljana Ristic</name></author><author><name sortKey="Vilimanovich, Urosh" sort="Vilimanovich, Urosh" uniqKey="Vilimanovich U" first="Urosh" last="Vilimanovich">Urosh Vilimanovich</name></author><author><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name></author><author><name sortKey="Sumarac Dumanovic, Mirjana" sort="Sumarac Dumanovic, Mirjana" uniqKey="Sumarac Dumanovic M" first="Mirjana" last="Sumarac-Dumanovic">Mirjana Sumarac-Dumanovic</name></author><author><name sortKey="Micic, Dragan" sort="Micic, Dragan" uniqKey="Micic D" first="Dragan" last="Micic">Dragan Micic</name></author><author><name sortKey="Bumbasirevic, Vladimir" sort="Bumbasirevic, Vladimir" uniqKey="Bumbasirevic V" first="Vladimir" last="Bumbasirevic">Vladimir Bumbasirevic</name></author><author><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:21871960</idno><idno type="pmid">21871960</idno><idno type="doi">10.1016/j.phrs.2011.08.003</idno><idno type="wicri:Area/Main/Corpus">001258</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001258</idno><idno type="wicri:Area/Main/Curation">001258</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001258</idno><idno 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Ljubica" sort="Vucicevic, Ljubica" uniqKey="Vucicevic L" first="Ljubica" last="Vucicevic">Ljubica Vucicevic</name></author><author><name sortKey="Tovilovic, Gordana" sort="Tovilovic, Gordana" uniqKey="Tovilovic G" first="Gordana" last="Tovilovic">Gordana Tovilovic</name></author><author><name sortKey="Ristic, Biljana" sort="Ristic, Biljana" uniqKey="Ristic B" first="Biljana" last="Ristic">Biljana Ristic</name></author><author><name sortKey="Vilimanovich, Urosh" sort="Vilimanovich, Urosh" uniqKey="Vilimanovich U" first="Urosh" last="Vilimanovich">Urosh Vilimanovich</name></author><author><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name></author><author><name sortKey="Sumarac Dumanovic, Mirjana" sort="Sumarac Dumanovic, Mirjana" uniqKey="Sumarac Dumanovic M" first="Mirjana" last="Sumarac-Dumanovic">Mirjana Sumarac-Dumanovic</name></author><author><name sortKey="Micic, Dragan" sort="Micic, Dragan" uniqKey="Micic D" first="Dragan" last="Micic">Dragan Micic</name></author><author><name sortKey="Bumbasirevic, Vladimir" sort="Bumbasirevic, Vladimir" uniqKey="Bumbasirevic V" first="Vladimir" last="Bumbasirevic">Vladimir Bumbasirevic</name></author><author><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name></author></analytic><series><title level="j">Pharmacological research</title><idno type="eISSN">1096-1186</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (antagonists & inhibitors)</term><term>AMP-Activated Protein Kinases (genetics)</term><term>AMP-Activated Protein Kinases (metabolism)</term><term>Animals (MeSH)</term><term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term><term>Apoptosis (drug effects)</term><term>Apoptosis Regulatory Proteins (metabolism)</term><term>Autophagy (drug effects)</term><term>Beclin-1 (MeSH)</term><term>Brain Neoplasms (enzymology)</term><term>Brain Neoplasms (genetics)</term><term>Brain Neoplasms (pathology)</term><term>Cell Line, Tumor (MeSH)</term><term>Cell Survival (drug effects)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Glioma (enzymology)</term><term>Glioma (genetics)</term><term>Glioma (pathology)</term><term>Humans (MeSH)</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)</term><term>Membrane Proteins (metabolism)</term><term>Mice (MeSH)</term><term>Microtubule-Associated Proteins (metabolism)</term><term>Protein Kinase Inhibitors (pharmacology)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>RNA Interference (MeSH)</term><term>Rats (MeSH)</term><term>Signal Transduction (drug effects)</term><term>Simvastatin (pharmacology)</term><term>TOR Serine-Threonine Kinases (metabolism)</term><term>Transfection (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>AMP-Activated Protein Kinases (antagonistes et inhibiteurs)</term><term>AMP-Activated Protein Kinases (génétique)</term><term>AMP-Activated Protein Kinases (métabolisme)</term><term>Animaux (MeSH)</term><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Autophagie (effets des médicaments et des substances chimiques)</term><term>Bécline-1 (MeSH)</term><term>Gliome (anatomopathologie)</term><term>Gliome (enzymologie)</term><term>Gliome (génétique)</term><term>Humains (MeSH)</term><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (pharmacologie)</term><term>Inhibiteurs de protéines kinases (pharmacologie)</term><term>Interférence par ARN (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Protocoles de polychimiothérapie antinéoplasique (pharmacologie)</term><term>Protéines associées aux microtubules (métabolisme)</term><term>Protéines membranaires (métabolisme)</term><term>Protéines proto-oncogènes c-akt (métabolisme)</term><term>Protéines régulatrices de l'apoptose (métabolisme)</term><term>Rats (MeSH)</term><term>Relation dose-effet des médicaments (MeSH)</term><term>Simvastatine (pharmacologie)</term><term>Souris (MeSH)</term><term>Survie cellulaire (effets des médicaments et des substances chimiques)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Transduction du signal (effets des médicaments et des substances chimiques)</term><term>Transfection (MeSH)</term><term>Tumeurs du cerveau (anatomopathologie)</term><term>Tumeurs du cerveau (enzymologie)</term><term>Tumeurs du cerveau (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>AMP-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>AMP-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term><term>Apoptosis Regulatory Proteins</term><term>Membrane Proteins</term><term>Microtubule-Associated Proteins</term><term>Proto-Oncogene Proteins c-akt</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Gliome</term><term>Tumeurs du cerveau</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>AMP-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>Cell Survival</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term><term>Autophagie</term><term>Survie cellulaire</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Gliome</term><term>Tumeurs du cerveau</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain Neoplasms</term><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Brain Neoplasms</term><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>AMP-Activated Protein Kinases</term><term>Gliome</term><term>Tumeurs du cerveau</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term><term>Protéines associées aux microtubules</term><term>Protéines membranaires</term><term>Protéines proto-oncogènes c-akt</term><term>Protéines régulatrices de l'apoptose</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain Neoplasms</term><term>Glioma</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase</term><term>Inhibiteurs de protéines kinases</term><term>Protocoles de polychimiothérapie antinéoplasique</term><term>Simvastatine</term></keywords><keywords scheme="MESH" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors</term><term>Protein Kinase Inhibitors</term><term>Simvastatin</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Beclin-1</term><term>Cell Line, Tumor</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Mice</term><term>RNA Interference</term><term>Rats</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Bécline-1</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Rats</term><term>Relation dose-effet des médicaments</term><term>Souris</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21871960</PMID><DateCompleted><Year>2012</Year><Month>05</Month><Day>15</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1096-1186</ISSN><JournalIssue CitedMedium="Internet"><Volume>65</Volume><Issue>1</Issue><PubDate><Year>2012</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Pharmacological research</Title><ISOAbbreviation>Pharmacol Res</ISOAbbreviation></Journal><ArticleTitle>Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin.</ArticleTitle><Pagination><MedlinePgn>111-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.phrs.2011.08.003</ELocationID><Abstract><AbstractText>The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.</AbstractText><CopyrightInformation>Copyright © 2011 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Misirkic</LastName><ForeName>Maja</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Janjetovic</LastName><ForeName>Kristina</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Vucicevic</LastName><ForeName>Ljubica</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Tovilovic</LastName><ForeName>Gordana</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Ristic</LastName><ForeName>Biljana</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Vilimanovich</LastName><ForeName>Urosh</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Harhaji-Trajkovic</LastName><ForeName>Ljubica</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Sumarac-Dumanovic</LastName><ForeName>Mirjana</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Micic</LastName><ForeName>Dragan</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Bumbasirevic</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Trajkovic</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>08</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Pharmacol Res</MedlineTA><NlmUniqueID>8907422</NlmUniqueID><ISSNLinking>1043-6618</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051017">Apoptosis Regulatory Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C491997">BECN1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000071186">Beclin-1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C115010">Becn1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C512829">Becn1 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019161">Hydroxymethylglutaryl-CoA Reductase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C526109">LC3 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C480860">MAP1LC3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008869">Microtubule-Associated Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C466626">light chain 3, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>AGG2FN16EV</RegistryNumber><NameOfSubstance UI="D019821">Simvastatin</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546845">mTOR protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.31</RegistryNumber><NameOfSubstance UI="D055372">AMP-Activated Protein Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D055372" MajorTopicYN="N">AMP-Activated Protein Kinases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051017" MajorTopicYN="N">Apoptosis Regulatory Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000071186" MajorTopicYN="N">Beclin-1</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001932" MajorTopicYN="N">Brain Neoplasms</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005910" MajorTopicYN="N">Glioma</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019161" MajorTopicYN="N">Hydroxymethylglutaryl-CoA Reductase Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008565" MajorTopicYN="N">Membrane Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008869" MajorTopicYN="N">Microtubule-Associated Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D034622" MajorTopicYN="N">RNA Interference</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019821" MajorTopicYN="N">Simvastatin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014162" MajorTopicYN="N">Transfection</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2011</Year><Month>05</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2011</Year><Month>08</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>08</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>8</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>8</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>5</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21871960</ArticleId><ArticleId IdType="pii">S1043-6618(11)00231-3</ArticleId><ArticleId IdType="doi">10.1016/j.phrs.2011.08.003</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Serbie</li></country></list><tree><noCountry><name sortKey="Bumbasirevic, Vladimir" sort="Bumbasirevic, Vladimir" uniqKey="Bumbasirevic V" first="Vladimir" last="Bumbasirevic">Vladimir Bumbasirevic</name><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name><name sortKey="Janjetovic, Kristina" sort="Janjetovic, Kristina" uniqKey="Janjetovic K" first="Kristina" last="Janjetovic">Kristina Janjetovic</name><name sortKey="Micic, Dragan" sort="Micic, Dragan" uniqKey="Micic D" first="Dragan" last="Micic">Dragan Micic</name><name sortKey="Ristic, Biljana" sort="Ristic, Biljana" uniqKey="Ristic B" first="Biljana" last="Ristic">Biljana Ristic</name><name sortKey="Sumarac Dumanovic, Mirjana" sort="Sumarac Dumanovic, Mirjana" uniqKey="Sumarac Dumanovic M" first="Mirjana" last="Sumarac-Dumanovic">Mirjana Sumarac-Dumanovic</name><name sortKey="Tovilovic, Gordana" sort="Tovilovic, Gordana" uniqKey="Tovilovic G" first="Gordana" last="Tovilovic">Gordana Tovilovic</name><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name><name sortKey="Vilimanovich, Urosh" sort="Vilimanovich, Urosh" uniqKey="Vilimanovich U" first="Urosh" last="Vilimanovich">Urosh Vilimanovich</name><name sortKey="Vucicevic, Ljubica" sort="Vucicevic, Ljubica" uniqKey="Vucicevic L" first="Ljubica" last="Vucicevic">Ljubica Vucicevic</name></noCountry><country name="Serbie"><noRegion><name sortKey="Misirkic, Maja" sort="Misirkic, Maja" uniqKey="Misirkic M" first="Maja" last="Misirkic">Maja Misirkic</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|area= RapamycinFungusV1
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|texte= Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin.
}}
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