AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.
Identifieur interne : 000397 ( Main/Exploration ); précédent : 000396; suivant : 000398AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.
Auteurs : Maja Jovanovic-Tucovic [Serbie] ; Ljubica Harhaji-Trajkovic [Serbie] ; Marija Dulovic [Allemagne] ; Gordana Tovilovic-Kovacevic [Serbie] ; Nevena Zogovic [Serbie] ; Marija Jeremic [Serbie] ; Milos Mandic [Serbie] ; Vladimir Kostic [Serbie] ; Vladimir Trajkovic [Serbie] ; Ivanka Markovic [Serbie]Source :
- European journal of pharmacology [ 1879-0712 ] ; 2019.
Descripteurs français
- KwdFr :
- 1-Méthyl-4-phényl-pyridinium (toxicité), AMP-Activated Protein Kinases (métabolisme), Activation enzymatique (effets des médicaments et des substances chimiques), Apoptose (effets des médicaments et des substances chimiques), Autophagie (effets des médicaments et des substances chimiques), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Humains (MeSH), Lignée cellulaire tumorale (MeSH), Protéines proto-oncogènes c-akt (métabolisme), Stress oxydatif (effets des médicaments et des substances chimiques).
- MESH :
- effets des médicaments et des substances chimiques : Activation enzymatique, Apoptose, Autophagie, Stress oxydatif.
- métabolisme : AMP-Activated Protein Kinases, Complexe-1 cible mécanistique de la rapamycine, Protéines proto-oncogènes c-akt.
- toxicité : 1-Méthyl-4-phényl-pyridinium.
- Humains, Lignée cellulaire tumorale.
English descriptors
- KwdEn :
- 1-Methyl-4-phenylpyridinium (toxicity), AMP-Activated Protein Kinases (metabolism), Apoptosis (drug effects), Autophagy (drug effects), Cell Line, Tumor (MeSH), Enzyme Activation (drug effects), Humans (MeSH), Mechanistic Target of Rapamycin Complex 1 (metabolism), Oxidative Stress (drug effects), Proto-Oncogene Proteins c-akt (metabolism).
- MESH :
- chemical , metabolism : AMP-Activated Protein Kinases, Mechanistic Target of Rapamycin Complex 1, Proto-Oncogene Proteins c-akt.
- chemical , toxicity : 1-Methyl-4-phenylpyridinium.
- drug effects : Apoptosis, Autophagy, Enzyme Activation, Oxidative Stress.
- Cell Line, Tumor, Humans.
Abstract
We investigated the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), prosurvival kinase Akt, oxidative stress, and autophagy in the cytotoxicity of parkinsonian neurotoxin 1-methyl-4-phenyl piridinium (MPP+) towards SH-SY5Y human neuroblastoma cells. MPP+-mediated oxidative stress, mitochondrial depolarization, and apoptotic cell death were associated with rapid (within 2 h) activation of AMPK, its target Raptor, and prosurvival kinase Akt. Antioxidants N-acetylcysteine and butylated hydroxyanisole suppressed MPP+-induced cytotoxicity, AMPK, and Akt activation. A genetic or pharmacological inhibition of AMPK increased MPP+-triggered production of reactive oxygen species and cell death, and diminished Akt phosphorylation, while AMPK activation protected SH-SY5Y cells from MPP+. On the other hand, genetic or pharmacological inactivation of Akt stimulated MPP+-triggered oxidative stress and neurotoxicity, but did not affect AMPK activation. At later time-points (16-24 h), MPP+ inhibited the main autophagy repressor mammalian target of rapamycin, which coincided with the increase in the levels of autophagy marker microtubule-associated protein 1 light-chain 3B. MPP+ also increased the concentration of a selective autophagic target sequestosome-1/p62 and reduced the levels of lysosomal-associated membrane protein 1 and cytoplasmic acidification, suggesting that MPP+-induced autophagy was coupled with a decrease in autophagic flux. Nevertheless, further pharmacological inhibition of autophagy sensitized SH-SY5Y cells to MPP+-induced death. Antioxidants and AMPK knockdown reduced, whereas genetic inactivation of Akt potentiated neurotoxin-triggered autophagy. These results suggest that MPP+-induced oxidative stress stimulates AMPK, which protects SH-SY5Y cells through early activation of antioxidative Akt and late induction of cytoprotective autophagy.
DOI: 10.1016/j.ejphar.2019.172677
PubMed: 31542478
Affiliations:
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Zogovic</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Jeremic, Marija" sort="Jeremic, Marija" uniqKey="Jeremic M" first="Marija" last="Jeremic">Marija Jeremic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Mandic, Milos" sort="Mandic, Milos" uniqKey="Mandic M" first="Milos" last="Mandic">Milos Mandic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Kostic, Vladimir" sort="Kostic, Vladimir" uniqKey="Kostic V" first="Vladimir" last="Kostic">Vladimir Kostic</name><affiliation wicri:level="1"><nlm:affiliation>Clinic for Neurology CCS, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Clinic for Neurology CCS, University of Belgrade, Dr Subotica 6, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia. Electronic address: vladimir.trajkovic@med.bg.ac.rs.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Markovic, Ivanka" sort="Markovic, Ivanka" uniqKey="Markovic I" first="Ivanka" last="Markovic">Ivanka Markovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia. Electronic address: ivanka.markovic@med.bg.ac.rs.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31542478</idno><idno type="pmid">31542478</idno><idno type="doi">10.1016/j.ejphar.2019.172677</idno><idno type="wicri:Area/Main/Corpus">000191</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000191</idno><idno type="wicri:Area/Main/Curation">000191</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000191</idno><idno type="wicri:Area/Main/Exploration">000191</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.</title><author><name sortKey="Jovanovic Tucovic, Maja" sort="Jovanovic Tucovic, Maja" uniqKey="Jovanovic Tucovic M" first="Maja" last="Jovanovic-Tucovic">Maja Jovanovic-Tucovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurophysiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd. 142, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Department of Neurophysiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd. 142, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Dulovic, Marija" sort="Dulovic, Marija" uniqKey="Dulovic M" first="Marija" last="Dulovic">Marija Dulovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, 23562, Lübeck, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, 23562, Lübeck</wicri:regionArea><wicri:noRegion>23562, Lübeck</wicri:noRegion><wicri:noRegion>23562, Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Tovilovic Kovacevic, Gordana" sort="Tovilovic Kovacevic, Gordana" uniqKey="Tovilovic Kovacevic G" first="Gordana" last="Tovilovic-Kovacevic">Gordana Tovilovic-Kovacevic</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Zogovic, Nevena" sort="Zogovic, Nevena" uniqKey="Zogovic N" first="Nevena" last="Zogovic">Nevena Zogovic</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Jeremic, Marija" sort="Jeremic, Marija" uniqKey="Jeremic M" first="Marija" last="Jeremic">Marija Jeremic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Mandic, Milos" sort="Mandic, Milos" uniqKey="Mandic M" first="Milos" last="Mandic">Milos Mandic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Kostic, Vladimir" sort="Kostic, Vladimir" uniqKey="Kostic V" first="Vladimir" last="Kostic">Vladimir Kostic</name><affiliation wicri:level="1"><nlm:affiliation>Clinic for Neurology CCS, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Clinic for Neurology CCS, University of Belgrade, Dr Subotica 6, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia. Electronic address: vladimir.trajkovic@med.bg.ac.rs.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author><author><name sortKey="Markovic, Ivanka" sort="Markovic, Ivanka" uniqKey="Markovic I" first="Ivanka" last="Markovic">Ivanka Markovic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia. Electronic address: ivanka.markovic@med.bg.ac.rs.</nlm:affiliation><country xml:lang="fr">Serbie</country><wicri:regionArea>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade</wicri:regionArea><wicri:noRegion>Belgrade</wicri:noRegion></affiliation></author></analytic><series><title level="j">European journal of pharmacology</title><idno type="eISSN">1879-0712</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenylpyridinium (toxicity)</term><term>AMP-Activated Protein Kinases (metabolism)</term><term>Apoptosis (drug effects)</term><term>Autophagy (drug effects)</term><term>Cell Line, Tumor (MeSH)</term><term>Enzyme Activation (drug effects)</term><term>Humans (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term><term>Oxidative Stress (drug effects)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>1-Méthyl-4-phényl-pyridinium (toxicité)</term><term>AMP-Activated Protein Kinases (métabolisme)</term><term>Activation enzymatique (effets des médicaments et des substances chimiques)</term><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Autophagie (effets des médicaments et des substances chimiques)</term><term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term><term>Humains (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Protéines proto-oncogènes c-akt (métabolisme)</term><term>Stress oxydatif (effets des médicaments et des substances chimiques)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term><term>Mechanistic Target of Rapamycin Complex 1</term><term>Proto-Oncogene Proteins c-akt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>1-Methyl-4-phenylpyridinium</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term><term>Enzyme Activation</term><term>Oxidative Stress</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Activation enzymatique</term><term>Apoptose</term><term>Autophagie</term><term>Stress oxydatif</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term><term>Complexe-1 cible mécanistique de la rapamycine</term><term>Protéines proto-oncogènes c-akt</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>1-Méthyl-4-phényl-pyridinium</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire tumorale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We investigated the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), prosurvival kinase Akt, oxidative stress, and autophagy in the cytotoxicity of parkinsonian neurotoxin 1-methyl-4-phenyl piridinium (MPP+) towards SH-SY5Y human neuroblastoma cells. MPP+-mediated oxidative stress, mitochondrial depolarization, and apoptotic cell death were associated with rapid (within 2 h) activation of AMPK, its target Raptor, and prosurvival kinase Akt. Antioxidants N-acetylcysteine and butylated hydroxyanisole suppressed MPP+-induced cytotoxicity, AMPK, and Akt activation. A genetic or pharmacological inhibition of AMPK increased MPP+-triggered production of reactive oxygen species and cell death, and diminished Akt phosphorylation, while AMPK activation protected SH-SY5Y cells from MPP+. On the other hand, genetic or pharmacological inactivation of Akt stimulated MPP+-triggered oxidative stress and neurotoxicity, but did not affect AMPK activation. At later time-points (16-24 h), MPP+ inhibited the main autophagy repressor mammalian target of rapamycin, which coincided with the increase in the levels of autophagy marker microtubule-associated protein 1 light-chain 3B. MPP+ also increased the concentration of a selective autophagic target sequestosome-1/p62 and reduced the levels of lysosomal-associated membrane protein 1 and cytoplasmic acidification, suggesting that MPP+-induced autophagy was coupled with a decrease in autophagic flux. Nevertheless, further pharmacological inhibition of autophagy sensitized SH-SY5Y cells to MPP+-induced death. Antioxidants and AMPK knockdown reduced, whereas genetic inactivation of Akt potentiated neurotoxin-triggered autophagy. These results suggest that MPP+-induced oxidative stress stimulates AMPK, which protects SH-SY5Y cells through early activation of antioxidative Akt and late induction of cytoprotective autophagy.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31542478</PMID><DateCompleted><Year>2020</Year><Month>03</Month><Day>23</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>23</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1879-0712</ISSN><JournalIssue CitedMedium="Internet"><Volume>863</Volume><PubDate><Year>2019</Year><Month>Nov</Month><Day>15</Day></PubDate></JournalIssue><Title>European journal of pharmacology</Title><ISOAbbreviation>Eur J Pharmacol</ISOAbbreviation></Journal><ArticleTitle>AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.</ArticleTitle><Pagination><MedlinePgn>172677</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0014-2999(19)30629-6</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejphar.2019.172677</ELocationID><Abstract><AbstractText>We investigated the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), prosurvival kinase Akt, oxidative stress, and autophagy in the cytotoxicity of parkinsonian neurotoxin 1-methyl-4-phenyl piridinium (MPP+) towards SH-SY5Y human neuroblastoma cells. MPP+-mediated oxidative stress, mitochondrial depolarization, and apoptotic cell death were associated with rapid (within 2 h) activation of AMPK, its target Raptor, and prosurvival kinase Akt. Antioxidants N-acetylcysteine and butylated hydroxyanisole suppressed MPP+-induced cytotoxicity, AMPK, and Akt activation. A genetic or pharmacological inhibition of AMPK increased MPP+-triggered production of reactive oxygen species and cell death, and diminished Akt phosphorylation, while AMPK activation protected SH-SY5Y cells from MPP+. On the other hand, genetic or pharmacological inactivation of Akt stimulated MPP+-triggered oxidative stress and neurotoxicity, but did not affect AMPK activation. At later time-points (16-24 h), MPP+ inhibited the main autophagy repressor mammalian target of rapamycin, which coincided with the increase in the levels of autophagy marker microtubule-associated protein 1 light-chain 3B. MPP+ also increased the concentration of a selective autophagic target sequestosome-1/p62 and reduced the levels of lysosomal-associated membrane protein 1 and cytoplasmic acidification, suggesting that MPP+-induced autophagy was coupled with a decrease in autophagic flux. Nevertheless, further pharmacological inhibition of autophagy sensitized SH-SY5Y cells to MPP+-induced death. Antioxidants and AMPK knockdown reduced, whereas genetic inactivation of Akt potentiated neurotoxin-triggered autophagy. These results suggest that MPP+-induced oxidative stress stimulates AMPK, which protects SH-SY5Y cells through early activation of antioxidative Akt and late induction of cytoprotective autophagy.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jovanovic-Tucovic</LastName><ForeName>Maja</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harhaji-Trajkovic</LastName><ForeName>Ljubica</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neurophysiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd. 142, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dulovic</LastName><ForeName>Marija</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Straße 1, 23562, Lübeck, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tovilovic-Kovacevic</LastName><ForeName>Gordana</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zogovic</LastName><ForeName>Nevena</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd 142, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeremic</LastName><ForeName>Marija</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mandic</LastName><ForeName>Milos</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kostic</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Clinic for Neurology CCS, University of Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trajkovic</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, University of Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia. Electronic address: vladimir.trajkovic@med.bg.ac.rs.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Markovic</LastName><ForeName>Ivanka</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Institute of Medical and Clinical Biochemistry, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia. Electronic address: ivanka.markovic@med.bg.ac.rs.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>09</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Eur J Pharmacol</MedlineTA><NlmUniqueID>1254354</NlmUniqueID><ISSNLinking>0014-2999</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</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><Chemical><RegistryNumber>R865A5OY8J</RegistryNumber><NameOfSubstance UI="D015655">1-Methyl-4-phenylpyridinium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015655" MajorTopicYN="N">1-Methyl-4-phenylpyridinium</DescriptorName><QualifierName UI="Q000633" MajorTopicYN="Y">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055372" MajorTopicYN="N">AMP-Activated Protein Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004789" MajorTopicYN="N">Enzyme Activation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018384" MajorTopicYN="N">Oxidative Stress</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">AMPK</Keyword><Keyword MajorTopicYN="N">Akt</Keyword><Keyword MajorTopicYN="N">Autophagy</Keyword><Keyword MajorTopicYN="N">MPP+</Keyword><Keyword MajorTopicYN="N">Neurons</Keyword><Keyword MajorTopicYN="N">Oxidative stress</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>07</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>09</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>09</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>3</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31542478</ArticleId><ArticleId IdType="pii">S0014-2999(19)30629-6</ArticleId><ArticleId IdType="doi">10.1016/j.ejphar.2019.172677</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>Serbie</li></country></list><tree><country name="Serbie"><noRegion><name sortKey="Jovanovic Tucovic, Maja" sort="Jovanovic Tucovic, Maja" uniqKey="Jovanovic Tucovic M" first="Maja" last="Jovanovic-Tucovic">Maja Jovanovic-Tucovic</name></noRegion><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name><name sortKey="Jeremic, Marija" sort="Jeremic, Marija" uniqKey="Jeremic M" first="Marija" last="Jeremic">Marija Jeremic</name><name sortKey="Kostic, Vladimir" sort="Kostic, Vladimir" uniqKey="Kostic V" first="Vladimir" last="Kostic">Vladimir Kostic</name><name sortKey="Mandic, Milos" sort="Mandic, Milos" uniqKey="Mandic M" first="Milos" last="Mandic">Milos Mandic</name><name sortKey="Markovic, Ivanka" sort="Markovic, Ivanka" uniqKey="Markovic I" first="Ivanka" last="Markovic">Ivanka Markovic</name><name sortKey="Tovilovic Kovacevic, Gordana" sort="Tovilovic Kovacevic, Gordana" uniqKey="Tovilovic Kovacevic G" first="Gordana" last="Tovilovic-Kovacevic">Gordana Tovilovic-Kovacevic</name><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name><name sortKey="Zogovic, Nevena" sort="Zogovic, Nevena" uniqKey="Zogovic N" first="Nevena" last="Zogovic">Nevena Zogovic</name></country><country name="Allemagne"><noRegion><name sortKey="Dulovic, Marija" sort="Dulovic, Marija" uniqKey="Dulovic M" first="Marija" last="Dulovic">Marija Dulovic</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy.
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