Coordination of frontline defense mechanisms under severe oxidative stress.
Mol Syst Biol
; 6: 393, 2010 Jul.
Article
en En
| MEDLINE
| ID: mdl-20664639
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxígeno
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Especies Reactivas de Oxígeno
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Estrés Oxidativo
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Halobacterium salinarum
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Proteínas Arqueales
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2010
Tipo del documento:
Article