Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.
Identifieur interne : 000775 ( Main/Exploration ); précédent : 000774; suivant : 000776Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.
Auteurs : Ramasamy Jagadeeswaran [États-Unis] ; Benjamin A. Vazquez [États-Unis] ; Muthusamy Thiruppathi [États-Unis] ; Balaji B. Ganesh [États-Unis] ; Vinzon Ibanez [États-Unis] ; Shuaiying Cui [États-Unis] ; James D. Engel [États-Unis] ; Alan M. Diamond [États-Unis] ; Robert E. Molokie [États-Unis] ; Joseph Desimone [États-Unis] ; Donald Lavelle [États-Unis] ; Angela Rivers [États-Unis]Source :
- Experimental hematology [ 1873-2399 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Drépanocytose (métabolisme), Espèces réactives de l'oxygène (métabolisme), Histone Demethylases (métabolisme), Humains (MeSH), Mitochondries (effets des médicaments et des substances chimiques), Mitochondries (métabolisme), Modèles animaux de maladie humaine (MeSH), Modèles biologiques (MeSH), Rhodamines (pharmacologie), Sirolimus (pharmacologie), Souris (MeSH), Spiranes (pharmacologie), Sérine-thréonine kinases TOR (métabolisme), Thiophènes (pharmacologie), Érythrocytes (effets des médicaments et des substances chimiques), Érythrocytes (métabolisme).
- MESH :
- effets des médicaments et des substances chimiques : Mitochondries, Érythrocytes.
- métabolisme : Drépanocytose, Espèces réactives de l'oxygène, Histone Demethylases, Mitochondries, Sérine-thréonine kinases TOR, Érythrocytes.
- pharmacologie : Rhodamines, Sirolimus, Spiranes, Thiophènes.
- Animaux, Humains, Modèles animaux de maladie humaine, Modèles biologiques, Souris.
English descriptors
- KwdEn :
- Anemia, Sickle Cell (metabolism), Animals (MeSH), Disease Models, Animal (MeSH), Erythrocytes (drug effects), Erythrocytes (metabolism), Histone Demethylases (metabolism), Humans (MeSH), Mice (MeSH), Mitochondria (drug effects), Mitochondria (metabolism), Models, Biological (MeSH), Reactive Oxygen Species (metabolism), Rhodamines (pharmacology), Sirolimus (pharmacology), Spiro Compounds (pharmacology), TOR Serine-Threonine Kinases (metabolism), Thiophenes (pharmacology).
- MESH :
- chemical , metabolism : Histone Demethylases, Reactive Oxygen Species, TOR Serine-Threonine Kinases.
- drug effects : Erythrocytes, Mitochondria.
- metabolism : Anemia, Sickle Cell, Erythrocytes, Mitochondria.
- chemical , pharmacology : Rhodamines, Sirolimus, Spiro Compounds, Thiophenes.
- Animals, Disease Models, Animal, Humans, Mice, Models, Biological.
Abstract
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.
DOI: 10.1016/j.exphem.2017.02.003
PubMed: 28238805
PubMed Central: PMC6263958
Affiliations:
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Le document en format XML
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Electronic address: riversa@uic.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28238805</idno><idno type="pmid">28238805</idno><idno type="doi">10.1016/j.exphem.2017.02.003</idno><idno type="pmc">PMC6263958</idno><idno type="wicri:Area/Main/Corpus">000869</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000869</idno><idno type="wicri:Area/Main/Curation">000869</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000869</idno><idno type="wicri:Area/Main/Exploration">000869</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.</title><author><name sortKey="Jagadeeswaran, Ramasamy" sort="Jagadeeswaran, Ramasamy" uniqKey="Jagadeeswaran R" first="Ramasamy" last="Jagadeeswaran">Ramasamy Jagadeeswaran</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Vazquez, Benjamin A" sort="Vazquez, Benjamin A" uniqKey="Vazquez B" first="Benjamin A" last="Vazquez">Benjamin A. Vazquez</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Thiruppathi, Muthusamy" sort="Thiruppathi, Muthusamy" uniqKey="Thiruppathi M" first="Muthusamy" last="Thiruppathi">Muthusamy Thiruppathi</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Ganesh, Balaji B" sort="Ganesh, Balaji B" uniqKey="Ganesh B" first="Balaji B" last="Ganesh">Balaji B. Ganesh</name><affiliation wicri:level="4"><nlm:affiliation>Research Resources Center, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research Resources Center, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Ibanez, Vinzon" sort="Ibanez, Vinzon" uniqKey="Ibanez V" first="Vinzon" last="Ibanez">Vinzon Ibanez</name><affiliation wicri:level="4"><nlm:affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Cui, Shuaiying" sort="Cui, Shuaiying" uniqKey="Cui S" first="Shuaiying" last="Cui">Shuaiying Cui</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, Boston University School of Medicine, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Boston University School of Medicine, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Engel, James D" sort="Engel, James D" uniqKey="Engel J" first="James D" last="Engel">James D. Engel</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Diamond, Alan M" sort="Diamond, Alan M" uniqKey="Diamond A" first="Alan M" last="Diamond">Alan M. Diamond</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Molokie, Robert E" sort="Molokie, Robert E" uniqKey="Molokie R" first="Robert E" last="Molokie">Robert E. Molokie</name><affiliation wicri:level="4"><nlm:affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Desimone, Joseph" sort="Desimone, Joseph" uniqKey="Desimone J" first="Joseph" last="Desimone">Joseph Desimone</name><affiliation wicri:level="4"><nlm:affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Lavelle, Donald" sort="Lavelle, Donald" uniqKey="Lavelle D" first="Donald" last="Lavelle">Donald Lavelle</name><affiliation wicri:level="4"><nlm:affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Rivers, Angela" sort="Rivers, Angela" uniqKey="Rivers A" first="Angela" last="Rivers">Angela Rivers</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA. Electronic address: riversa@uic.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author></analytic><series><title level="j">Experimental hematology</title><idno type="eISSN">1873-2399</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anemia, Sickle Cell (metabolism)</term><term>Animals (MeSH)</term><term>Disease Models, Animal (MeSH)</term><term>Erythrocytes (drug effects)</term><term>Erythrocytes (metabolism)</term><term>Histone Demethylases (metabolism)</term><term>Humans (MeSH)</term><term>Mice (MeSH)</term><term>Mitochondria (drug effects)</term><term>Mitochondria (metabolism)</term><term>Models, Biological (MeSH)</term><term>Reactive Oxygen Species (metabolism)</term><term>Rhodamines (pharmacology)</term><term>Sirolimus (pharmacology)</term><term>Spiro Compounds (pharmacology)</term><term>TOR Serine-Threonine Kinases (metabolism)</term><term>Thiophenes (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Drépanocytose (métabolisme)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Histone Demethylases (métabolisme)</term><term>Humains (MeSH)</term><term>Mitochondries (effets des médicaments et des substances chimiques)</term><term>Mitochondries (métabolisme)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Modèles biologiques (MeSH)</term><term>Rhodamines (pharmacologie)</term><term>Sirolimus (pharmacologie)</term><term>Souris (MeSH)</term><term>Spiranes (pharmacologie)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Thiophènes (pharmacologie)</term><term>Érythrocytes (effets des médicaments et des substances chimiques)</term><term>Érythrocytes (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Histone Demethylases</term><term>Reactive Oxygen Species</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Erythrocytes</term><term>Mitochondria</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Mitochondries</term><term>Érythrocytes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Anemia, Sickle Cell</term><term>Erythrocytes</term><term>Mitochondria</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Drépanocytose</term><term>Espèces réactives de l'oxygène</term><term>Histone Demethylases</term><term>Mitochondries</term><term>Sérine-thréonine kinases TOR</term><term>Érythrocytes</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Rhodamines</term><term>Sirolimus</term><term>Spiranes</term><term>Thiophènes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Rhodamines</term><term>Sirolimus</term><term>Spiro Compounds</term><term>Thiophenes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Mice</term><term>Models, Biological</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Modèles biologiques</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28238805</PMID><DateCompleted><Year>2017</Year><Month>09</Month><Day>26</Day></DateCompleted><DateRevised><Year>2020</Year><Month>01</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-2399</ISSN><JournalIssue CitedMedium="Internet"><Volume>50</Volume><PubDate><Year>2017</Year><Month>06</Month></PubDate></JournalIssue><Title>Experimental hematology</Title><ISOAbbreviation>Exp Hematol</ISOAbbreviation></Journal><ArticleTitle>Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.</ArticleTitle><Pagination><MedlinePgn>46-52</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0301-472X(17)30062-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.exphem.2017.02.003</ELocationID><Abstract><AbstractText>Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.</AbstractText><CopyrightInformation>Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jagadeeswaran</LastName><ForeName>Ramasamy</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vazquez</LastName><ForeName>Benjamin A</ForeName><Initials>BA</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thiruppathi</LastName><ForeName>Muthusamy</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ganesh</LastName><ForeName>Balaji B</ForeName><Initials>BB</Initials><AffiliationInfo><Affiliation>Research Resources Center, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ibanez</LastName><ForeName>Vinzon</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cui</LastName><ForeName>Shuaiying</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medicine, Boston University School of Medicine, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Engel</LastName><ForeName>James D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diamond</LastName><ForeName>Alan M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Molokie</LastName><ForeName>Robert E</ForeName><Initials>RE</Initials><AffiliationInfo><Affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>DeSimone</LastName><ForeName>Joseph</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lavelle</LastName><ForeName>Donald</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rivers</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA. Electronic address: riversa@uic.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R03 HL135453</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 HL114561</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U01 HL117658</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K01 HL103172</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R03 HL135454</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Exp Hematol</MedlineTA><NlmUniqueID>0402313</NlmUniqueID><ISSNLinking>0301-472X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C547335">RN1 compound</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012235">Rhodamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013141">Spiro Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013876">Thiophenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.11.-</RegistryNumber><NameOfSubstance UI="D056466">Histone Demethylases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.5.-</RegistryNumber><NameOfSubstance UI="C495195">KDM1A protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber><NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000755" MajorTopicYN="N">Anemia, Sickle Cell</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004912" MajorTopicYN="N">Erythrocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056466" MajorTopicYN="N">Histone Demethylases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008928" MajorTopicYN="N">Mitochondria</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008954" MajorTopicYN="N">Models, Biological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017382" MajorTopicYN="N">Reactive Oxygen Species</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012235" MajorTopicYN="N">Rhodamines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013141" MajorTopicYN="N">Spiro Compounds</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013876" MajorTopicYN="N">Thiophenes</DescriptorName><QualifierName UI="Q000494" 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IdType="pubmed">26858356</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Massachusetts</li><li>Michigan</li></region><settlement><li>Chicago</li></settlement><orgName><li>Université de l'Illinois à Chicago</li></orgName></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Jagadeeswaran, Ramasamy" sort="Jagadeeswaran, Ramasamy" uniqKey="Jagadeeswaran R" first="Ramasamy" last="Jagadeeswaran">Ramasamy Jagadeeswaran</name></region><name sortKey="Cui, Shuaiying" sort="Cui, Shuaiying" uniqKey="Cui S" first="Shuaiying" last="Cui">Shuaiying Cui</name><name sortKey="Desimone, Joseph" sort="Desimone, Joseph" uniqKey="Desimone J" first="Joseph" last="Desimone">Joseph Desimone</name><name sortKey="Diamond, Alan M" sort="Diamond, Alan M" uniqKey="Diamond A" first="Alan M" last="Diamond">Alan M. Diamond</name><name sortKey="Engel, James D" sort="Engel, James D" uniqKey="Engel J" first="James D" last="Engel">James D. Engel</name><name sortKey="Ganesh, Balaji B" sort="Ganesh, Balaji B" uniqKey="Ganesh B" first="Balaji B" last="Ganesh">Balaji B. Ganesh</name><name sortKey="Ibanez, Vinzon" sort="Ibanez, Vinzon" uniqKey="Ibanez V" first="Vinzon" last="Ibanez">Vinzon Ibanez</name><name sortKey="Lavelle, Donald" sort="Lavelle, Donald" uniqKey="Lavelle D" first="Donald" last="Lavelle">Donald Lavelle</name><name sortKey="Molokie, Robert E" sort="Molokie, Robert E" uniqKey="Molokie R" first="Robert E" last="Molokie">Robert E. Molokie</name><name sortKey="Rivers, Angela" sort="Rivers, Angela" uniqKey="Rivers A" first="Angela" last="Rivers">Angela Rivers</name><name sortKey="Thiruppathi, Muthusamy" sort="Thiruppathi, Muthusamy" uniqKey="Thiruppathi M" first="Muthusamy" last="Thiruppathi">Muthusamy Thiruppathi</name><name sortKey="Vazquez, Benjamin A" sort="Vazquez, Benjamin A" uniqKey="Vazquez B" first="Benjamin A" last="Vazquez">Benjamin A. Vazquez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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