Global disruption of cell cycle progression and nutrient response by the antifungal agent amiodarone.
Identifieur interne : 001728 ( Main/Exploration ); précédent : 001727; suivant : 001729Global disruption of cell cycle progression and nutrient response by the antifungal agent amiodarone.
Auteurs : Yong-Qiang Zhang [États-Unis] ; Rajini RaoSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2007.
Descripteurs français
- KwdFr :
- Amiodarone (pharmacologie), Antifongiques (pharmacologie), Calcineurine (pharmacologie), Calcium (métabolisme), Chlorure de calcium (pharmacologie), Cycle cellulaire (MeSH), Délétion de gène (MeSH), Facteurs de transcription (MeSH), Microscopie de fluorescence (MeSH), Modèles biologiques (MeSH), Mutation (MeSH), Protéines de Saccharomyces cerevisiae (métabolisme), Protéines de liaison à l'ADN (MeSH), Relation dose-effet des médicaments (MeSH), Régulation de l'expression des gènes fongiques (MeSH), Saccharomyces cerevisiae (métabolisme), Séquençage par oligonucléotides en batterie (MeSH), Transactivateurs (métabolisme), Transcription génétique (MeSH).
- MESH :
- métabolisme : Calcium, Protéines de Saccharomyces cerevisiae, Saccharomyces cerevisiae, Transactivateurs.
- pharmacologie : Amiodarone, Antifongiques, Calcineurine, Chlorure de calcium.
- Cycle cellulaire, Délétion de gène, Facteurs de transcription, Microscopie de fluorescence, Modèles biologiques, Mutation, Protéines de liaison à l'ADN, Relation dose-effet des médicaments, Régulation de l'expression des gènes fongiques, Séquençage par oligonucléotides en batterie, Transcription génétique.
English descriptors
- KwdEn :
- Amiodarone (pharmacology), Antifungal Agents (pharmacology), Calcineurin (pharmacology), Calcium (metabolism), Calcium Chloride (pharmacology), Cell Cycle (MeSH), DNA-Binding Proteins (MeSH), Dose-Response Relationship, Drug (MeSH), Gene Deletion (MeSH), Gene Expression Regulation, Fungal (MeSH), Microscopy, Fluorescence (MeSH), Models, Biological (MeSH), Mutation (MeSH), Oligonucleotide Array Sequence Analysis (MeSH), Saccharomyces cerevisiae (metabolism), Saccharomyces cerevisiae Proteins (metabolism), Trans-Activators (metabolism), Transcription Factors (MeSH), Transcription, Genetic (MeSH).
- MESH :
- chemical , metabolism : Calcium, Saccharomyces cerevisiae Proteins, Trans-Activators.
- chemical , pharmacology : Amiodarone, Antifungal Agents, Calcineurin, Calcium Chloride.
- metabolism : Saccharomyces cerevisiae.
- Cell Cycle, DNA-Binding Proteins, Dose-Response Relationship, Drug, Gene Deletion, Gene Expression Regulation, Fungal, Microscopy, Fluorescence, Models, Biological, Mutation, Oligonucleotide Array Sequence Analysis, Transcription Factors, Transcription, Genetic.
Abstract
The antiarrhythmic drug amiodarone has fungicidal activity against a broad range of fungi. In Saccharomyces cerevisiae, it elicits an immediate influx of Ca(2+) followed by mitochondrial fragmentation and eventual cell death. To dissect the mechanism of its toxicity, we assessed the transcriptional response of S. cerevisiae to amiodarone by DNA microarray. Consistent with the drug-induced calcium burst, more than half of the differentially transcribed genes were induced by high levels of CaCl(2). Amiodarone also caused rapid nuclear accumulation of the calcineurin-regulated Crz1. The majority of genes induced by amiodarone within 10 min were involved in utilization of alternative carbon and nitrogen sources and in mobilizing energy reserves. The similarity to nutrient starvation responses seen in stationary phase cells, rapamycin treatment, and late stages of shift to diauxic conditions and nitrogen depletion suggests that amiodarone may interfere with nutrient sensing and regulatory networks. Transcription of a set of nutrient-responsive genes was affected by amiodarone but not CaCl(2), indicating that activation of the starvation response was independent of Ca(2+). Genes down-regulated by amiodarone were involved in all stages of cell cycle control. A moderate dose of amiodarone temporarily delayed cell cycle progression at G(1), S, and G(2)/M phases, with the Swe1-mediated delay in G(2)/M phase being most prominent in a calcineurin-dependent manner. Overall, the transcriptional responses to amiodarone revealed by this study were found to be distinct from other classes of antifungals, including the azole drugs, pointing toward a novel target pathway in combating fungal pathogenesis.
DOI: 10.1074/jbc.M707593200
PubMed: 17974566
Affiliations:
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xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Rao, Rajini" sort="Rao, Rajini" uniqKey="Rao R" first="Rajini" last="Rao">Rajini Rao</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amiodarone (pharmacology)</term><term>Antifungal Agents (pharmacology)</term><term>Calcineurin (pharmacology)</term><term>Calcium (metabolism)</term><term>Calcium Chloride (pharmacology)</term><term>Cell Cycle (MeSH)</term><term>DNA-Binding Proteins (MeSH)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Gene Deletion (MeSH)</term><term>Gene Expression Regulation, Fungal (MeSH)</term><term>Microscopy, Fluorescence (MeSH)</term><term>Models, Biological (MeSH)</term><term>Mutation (MeSH)</term><term>Oligonucleotide Array Sequence Analysis (MeSH)</term><term>Saccharomyces cerevisiae (metabolism)</term><term>Saccharomyces cerevisiae Proteins (metabolism)</term><term>Trans-Activators (metabolism)</term><term>Transcription Factors (MeSH)</term><term>Transcription, Genetic (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amiodarone (pharmacologie)</term><term>Antifongiques (pharmacologie)</term><term>Calcineurine (pharmacologie)</term><term>Calcium (métabolisme)</term><term>Chlorure de calcium (pharmacologie)</term><term>Cycle cellulaire (MeSH)</term><term>Délétion de gène (MeSH)</term><term>Facteurs de transcription (MeSH)</term><term>Microscopie de fluorescence (MeSH)</term><term>Modèles biologiques (MeSH)</term><term>Mutation (MeSH)</term><term>Protéines de Saccharomyces cerevisiae (métabolisme)</term><term>Protéines de liaison à l'ADN (MeSH)</term><term>Relation dose-effet des médicaments (MeSH)</term><term>Régulation de l'expression des gènes fongiques (MeSH)</term><term>Saccharomyces cerevisiae (métabolisme)</term><term>Séquençage par oligonucléotides en batterie (MeSH)</term><term>Transactivateurs (métabolisme)</term><term>Transcription génétique (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term><term>Saccharomyces cerevisiae Proteins</term><term>Trans-Activators</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amiodarone</term><term>Antifungal Agents</term><term>Calcineurin</term><term>Calcium Chloride</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcium</term><term>Protéines de Saccharomyces cerevisiae</term><term>Saccharomyces cerevisiae</term><term>Transactivateurs</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Amiodarone</term><term>Antifongiques</term><term>Calcineurine</term><term>Chlorure de calcium</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Cycle</term><term>DNA-Binding Proteins</term><term>Dose-Response Relationship, Drug</term><term>Gene Deletion</term><term>Gene Expression Regulation, Fungal</term><term>Microscopy, Fluorescence</term><term>Models, Biological</term><term>Mutation</term><term>Oligonucleotide Array Sequence Analysis</term><term>Transcription Factors</term><term>Transcription, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cycle cellulaire</term><term>Délétion de gène</term><term>Facteurs de transcription</term><term>Microscopie de fluorescence</term><term>Modèles biologiques</term><term>Mutation</term><term>Protéines de liaison à l'ADN</term><term>Relation dose-effet des médicaments</term><term>Régulation de l'expression des gènes fongiques</term><term>Séquençage par oligonucléotides en batterie</term><term>Transcription génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The antiarrhythmic drug amiodarone has fungicidal activity against a broad range of fungi. In Saccharomyces cerevisiae, it elicits an immediate influx of Ca(2+) followed by mitochondrial fragmentation and eventual cell death. To dissect the mechanism of its toxicity, we assessed the transcriptional response of S. cerevisiae to amiodarone by DNA microarray. Consistent with the drug-induced calcium burst, more than half of the differentially transcribed genes were induced by high levels of CaCl(2). Amiodarone also caused rapid nuclear accumulation of the calcineurin-regulated Crz1. The majority of genes induced by amiodarone within 10 min were involved in utilization of alternative carbon and nitrogen sources and in mobilizing energy reserves. The similarity to nutrient starvation responses seen in stationary phase cells, rapamycin treatment, and late stages of shift to diauxic conditions and nitrogen depletion suggests that amiodarone may interfere with nutrient sensing and regulatory networks. Transcription of a set of nutrient-responsive genes was affected by amiodarone but not CaCl(2), indicating that activation of the starvation response was independent of Ca(2+). Genes down-regulated by amiodarone were involved in all stages of cell cycle control. A moderate dose of amiodarone temporarily delayed cell cycle progression at G(1), S, and G(2)/M phases, with the Swe1-mediated delay in G(2)/M phase being most prominent in a calcineurin-dependent manner. Overall, the transcriptional responses to amiodarone revealed by this study were found to be distinct from other classes of antifungals, including the azole drugs, pointing toward a novel target pathway in combating fungal pathogenesis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17974566</PMID><DateCompleted><Year>2008</Year><Month>03</Month><Day>04</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0021-9258</ISSN><JournalIssue CitedMedium="Print"><Volume>282</Volume><Issue>52</Issue><PubDate><Year>2007</Year><Month>Dec</Month><Day>28</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J Biol Chem</ISOAbbreviation></Journal><ArticleTitle>Global disruption of cell cycle progression and nutrient response by the antifungal agent amiodarone.</ArticleTitle><Pagination><MedlinePgn>37844-53</MedlinePgn></Pagination><Abstract><AbstractText>The antiarrhythmic drug amiodarone has fungicidal activity against a broad range of fungi. In Saccharomyces cerevisiae, it elicits an immediate influx of Ca(2+) followed by mitochondrial fragmentation and eventual cell death. To dissect the mechanism of its toxicity, we assessed the transcriptional response of S. cerevisiae to amiodarone by DNA microarray. Consistent with the drug-induced calcium burst, more than half of the differentially transcribed genes were induced by high levels of CaCl(2). Amiodarone also caused rapid nuclear accumulation of the calcineurin-regulated Crz1. The majority of genes induced by amiodarone within 10 min were involved in utilization of alternative carbon and nitrogen sources and in mobilizing energy reserves. The similarity to nutrient starvation responses seen in stationary phase cells, rapamycin treatment, and late stages of shift to diauxic conditions and nitrogen depletion suggests that amiodarone may interfere with nutrient sensing and regulatory networks. Transcription of a set of nutrient-responsive genes was affected by amiodarone but not CaCl(2), indicating that activation of the starvation response was independent of Ca(2+). Genes down-regulated by amiodarone were involved in all stages of cell cycle control. A moderate dose of amiodarone temporarily delayed cell cycle progression at G(1), S, and G(2)/M phases, with the Swe1-mediated delay in G(2)/M phase being most prominent in a calcineurin-dependent manner. Overall, the transcriptional responses to amiodarone revealed by this study were found to be distinct from other classes of antifungals, including the azole drugs, pointing toward a novel target pathway in combating fungal pathogenesis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yong-Qiang</ForeName><Initials>YQ</Initials><AffiliationInfo><Affiliation>Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rao</LastName><ForeName>Rajini</ForeName><Initials>R</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI065983</GrantID><Acronym>AI</Acronym><Agency>NIAID 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>2007</Year><Month>11</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Biol Chem</MedlineTA><NlmUniqueID>2985121R</NlmUniqueID><ISSNLinking>0021-9258</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000935">Antifungal Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C109868">CRZ1 protein, S cerevisiae</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004268">DNA-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029701">Saccharomyces cerevisiae Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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IdType="pubmed">17974566</ArticleId><ArticleId IdType="pii">M707593200</ArticleId><ArticleId IdType="doi">10.1074/jbc.M707593200</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Rao, Rajini" sort="Rao, Rajini" uniqKey="Rao R" first="Rajini" last="Rao">Rajini Rao</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Zhang, Yong Qiang" sort="Zhang, Yong Qiang" uniqKey="Zhang Y" first="Yong-Qiang" last="Zhang">Yong-Qiang Zhang</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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