title: Coordination of frontline defense mechanisms under severe oxidative stress.
abstract: Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98103, USA.
authors.forename: Amardeep
authors.initials: A
authors.lastname: Kaur
authors.forename: Phu T
authors.initials: PT
authors.lastname: Van
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Busch
authors.forename: Courtney K
authors.initials: CK
authors.lastname: Robinson
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.forename: Wyming Lee
authors.initials: WL
authors.lastname: Pang
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiss
authors.forename: Jocelyne
authors.initials: J
authors.lastname: DiRuggiero
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
mesh_terms: D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism*; D002338:Carotenoids / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019848:Gene Expression Regulation, Archaeal; D005838:Genotype; D019617:Halobacterium salinarum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000378:metabolism*; D010269:Paraquat / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*; D025604:Rhodopsins, Microbial / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D019843:Archaeal Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D025604:Rhodopsins, Microbial; D013481:Superoxides; D002338:Carotenoids; D006861:Hydrogen Peroxide; D010544:Peroxidases; D002374:Catalase; D013482:Superoxide Dismutase; D010269:Paraquat; D010100:Oxygen