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Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans.

Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Research Abstract Details 

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  • Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Abstract Text:

    hyeseung leeHyeseung Lee,clara m bienClara M Bien,adam l hughesAdam L Hughes,peter j espenshadePeter J Espenshade,kyung j kwon-chungKyung J Kwon-Chung,yun c changYun C Chang,

    We investigated the effects of the hypoxia-mimetic CoCl2 in the pathogenic fungus Cryptococcus neoformans and demonstrated that CoCl2 leads to defects in several enzymatic steps in ergosterol biosynthesis. Sterol defects were amplified in cells lacking components of the Sre1p-mediated oxygen-sensing pathway. Consequently, Sre1p and its binding partner Scp1p were essential for growth in the presence of CoCl2. Interestingly, high copies of a single gene involved in ergosterol biosynthesis, ERG25, rescued this growth defect. We show that the inhibitory effect of CoCl2 on scp1Delta and sre1Delta cells likely resulted from either an accumulation of non-viable methylated sterols or a decrease in the amount of ergosterol. Similar findings were also observed in the ascomycetous yeast, Schizosaccharomyces pombe, suggesting that the effects of CoCl2 on the Sre1p-mediated response are conserved in fungi. In addition, gene expression analysis revealed limited overlap between Sre1p-dependant gene activation in the presence of CoCl2 and low oxygen. The majority of genes similarly affected by both CoCl2 and low oxygen were involved in ergosterol synthesis and in iron/copper transport. This article identifies the Sre1p pathway as a common mechanism by which yeast cells sense and adapt to changes in both CoCl2 concentrations and oxygen levels.

    Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Publishing Authors By Initials

    h leeH Lee,cm bienCM Bien,al hughesAL Hughes,pj espenshadePJ Espenshade,kj kwon-chungKJ Kwon-Chung,yc changYC Chang,

    For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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    Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Molecular microbiology

    VOLUME: 65

    Page Numbers: 1018-33

    Journal Abbreviation: Mol. Microbiol.

    ISSN: 0950-382X

    DAY: 21

    MONTH: 07

    YEAR: 2007

    Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8712028

    Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Keywords Mesh Terms:

    KEYWORDS: Up-Regulation

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Information

    Substance Name: cobaltous chloride

    Registry Number: 7646-79-9

    Grant and Affiliation Information for Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans.

    AFFILIATION: Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NHLBI

    GRANT: HL077588

    ACRONYM: HL

    MEDLINETA: Mol Microbiol

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