{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895649377152.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0907213106"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0907213106"}}],"dc:title":[{"@value":"OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional mechanisms"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Oxidative stress has been implicated in diverse disease states and aging. To date, induction of cellular responses to combat oxidative stress has been characterized largely at the transcriptional level, with emphasis on Nrf2-mediated activation of antioxidant response elements. In this study, we demonstrate that OLA1, a novel Obg-like ATPase, functions as a negative regulator of the cellular antioxidant response independent of transcriptional processes. Knockdown of OLA1 in human cells elicited an increased resistance to oxidizing agents including<jats:italic>tert</jats:italic>-butyl hydroperoxide (tBH) and diamide without affecting cell proliferation, baseline apoptosis, or sensitivity to other cytotoxic agents that target the mitochondria, cytoskeleton, or DNA. Conversely, overexpression of OLA1 increased cellular sensitivity to tBH and diamide. When challenged with oxidants, OLA1-knockdown cells had decreased production of intracellular reactive oxygen species and exhibited less depletion of reduced glutathione. Surprisingly, knockdown of OLA1 caused only minimal genomic response; no changes were found in the mRNA levels of genes encoding antioxidant enzymes, enzymes that produce antioxidants (including glutathione), or other genes known to respond to Nrf2. Moreover, when de novo protein synthesis was blocked by cycloheximide in OLA1-knockdown cells, they continued to demonstrate increased resistance to both tBH and diamide. These data demonstrate that OLA1 suppresses the antioxidant response through nontranscriptional mechanisms. The beneficial effects observed upon OLA1-knockdown suggest that this regulatory ATPase is a potential novel target for antioxidative therapy.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380857672207013762","@type":"Researcher","foaf:name":[{"@value":"Jiawei Zhang"}],"jpcoar:affiliationName":[{"@value":"The Methodist Hospital Research Institute, and the Departments of aRadiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857672207013761","@type":"Researcher","foaf:name":[{"@value":"Valentina Rubio"}],"jpcoar:affiliationName":[{"@value":"The Methodist Hospital Research Institute, and the Departments of aRadiology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857672207013760","@type":"Researcher","foaf:name":[{"@value":"Michael W. Lieberman"}],"jpcoar:affiliationName":[{"@value":"Pathology, The Methodist Hospital, Houston, TX 77030"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857672207013763","@type":"Researcher","foaf:name":[{"@value":"Zheng-Zheng Shi"}],"jpcoar:affiliationName":[{"@value":"The Methodist Hospital Research Institute, and the Departments of aRadiology and"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2009-09-08","prism:volume":"106","prism:number":"36","prism:startingPage":"15356","prism:endingPage":"15361"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0907213106"}],"createdAt":"2009-08-25","modifiedAt":"2023-05-26","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360565168158934656","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Functional characterization of <i>ObgC</i> in ribosome biogenesis during chloroplast development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846641009995520","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The BRCA1/BARD1-Interacting Protein OLA1 Functions in Centrosome Regulation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567782028800","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of Haemaphysalis longicornis Genes Differentially Expressed in Response to Babesia microti Infection"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861707160292736","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"OLA-1, an Obg-like ATPase, integrates hunger with temperature information in sensory neurons in C. elegans"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.0907213106"},{"@type":"CROSSREF","@value":"10.1111/j.1365-313x.2012.04976.x_references_DOI_2o5PJF41WD3nfGTUMQsA2qV4szd"},{"@type":"CROSSREF","@value":"10.3390/pathogens9050378_references_DOI_2o5PJF41WD3nfGTUMQsA2qV4szd"},{"@type":"CROSSREF","@value":"10.1371/journal.pgen.1010219_references_DOI_2o5PJF41WD3nfGTUMQsA2qV4szd"},{"@type":"CROSSREF","@value":"10.1016/j.molcel.2013.10.028_references_DOI_2o5PJF41WD3nfGTUMQsA2qV4szd"}]}