title: Nitric oxide-mediated antioxidative mechanism in yeast through the activation of the transcription factor Mac1.
abstract: The budding yeast Saccharomyces cerevisiae possesses various defense mechanisms against environmental stresses that generate reactive oxygen species, leading to growth inhibition or cell death. Our recent study showed a novel antioxidative mechanism mediated by nitric oxide (NO) in yeast cells, but the mechanism underlying the oxidative stress tolerance remained unclear. We report here one of the downstream pathways of NO involved in stress-tolerance mechanism in yeast. Our microarray and real-time quantitative PCR analyses revealed that exogenous NO treatment induced the expression of genes responsible for copper metabolism under the control of the transcription factor Mac1, including the CTR1 gene encoding high-affinity copper transporter. Our ChIP analysis also demonstrated that exogenous NO enhances the binding of Mac1 to the promoter region of target genes. Interestingly, we found that NO produced under high-temperature stress conditions increased the transcription level of the CTR1 gene. Furthermore, NO produced during exposure to high temperature also increased intracellular copper content, the activity of Cu,Zn-superoxide dismutase Sod1, and cell viability after exposure to high-temperature in a manner dependent on Mac1. NO did not affect the expression of the MAC1 gene, indicating that NO activates Mac1 through its post-translational modification. Based on the results shown here, we propose a novel NO-mediated antioxidative mechanism that Mac1 activated by NO induces the CTR1 gene, leading to an increase in cellular copper level, and then Cu(I) activates Sod1. This is the first report to unveil the mechanism of NO-dependent antioxidative system in yeast.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nasuno
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Aitoku
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Manago
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sasano
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D005800:Genes, Fungal; D006358:Hot Temperature; D009569:Nitric Oxide / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C084954:MAC1 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D009569:Nitric Oxide; D013482:Superoxide Dismutase