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Cord blood genomic analysis highlights the role of redox balance.

ABSTRACT: Neonates are exposed to elevated levels of reactive oxygen species as they transition from a hypoxic intrauterine to a normoxic extrauterine environment at birth. This increased oxidative stress is associated with neonatal morbidity. Current antioxidant supplementation treatment strategies have yet to translate into improved neonatal outcomes. Our understanding of a newborn's intricate redox balance, particularly at the genomic level, remains limited. Here, we performed genomic microarray analyses (approximately 14,500 genes) on extracted mRNA from umbilical cord whole blood at term gestation (n=10). Bioinformatic analyses identified 282 genes (2.0%) that were consistently present within the highest quintile of expressed genes. These genes were highly associated with oxidant stress and included superoxide dismutase 1, catalase, peroxiredoxins, and uncoupling proteins. Pathway analyses identified statistically significantly overrepresented functional pathways including "oxidative stress," "oxidative stress response mediated by nuclear factor-erythroid 2-related factor," "hypoxia-inducible factor signaling," and "mitochondrial dysfunction" (p<0.05). These results suggest that neonates require high levels of antioxidants and an intricate cellular redox balance to ensure a successful transition to the extrauterine environment. Understanding the genes necessary to maintain this delicate redox balance may lead to the development of alternative treatment strategies.

SUBMITTER: Maron JL

PROVIDER: S-EPMC2921475 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Cord blood genomic analysis highlights the role of redox balance.

Maron Jill L JL Johnson Kirby L KL Parkin Christopher C Iyer Lakshamanan L Davis Jonathan M JM Bianchi Diana W DW

Free radical biology & medicine 20100608 6

Neonates are exposed to elevated levels of reactive oxygen species as they transition from a hypoxic intrauterine to a normoxic extrauterine environment at birth. This increased oxidative stress is associated with neonatal morbidity. Current antioxidant supplementation treatment strategies have yet to translate into improved neonatal outcomes. Our understanding of a newborn's intricate redox balance, particularly at the genomic level, remains limited. Here, we performed genomic microarray analys ...[more]

PMID: 20566327

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Project description:Diatoms are unicellular photosynthetic algae known to secrete organic matter that fuels secondary production in the ocean, though our knowledge of how their physiology impacts the composition of dissolved organic matter remains limited. Like all photosynthetic organisms, their use of light for energy and reducing power creates the challenge of avoiding cellular damage. To better understand the interplay between redox balance and organic matter secretion, we reconstructed a genome-scale metabolic model of Thalassiosira pseudonana strain CCMP 1335, a model for diatom molecular biology and physiology, with a 60-year history of studies. The model simulates the metabolic activities of 1,432 genes via a network of 2,792 metabolites produced through 6,079 reactions distributed across six subcellular compartments. Growth was simulated under different steady-state light conditions (5-200 μmol photons m-2 s-1) and in a batch culture progressing from exponential growth to nitrate-limitation and nitrogen-starvation. We used the model to examine the dissipation of reductants generated through light-dependent processes and found that when available, nitrate assimilation is an important means of dissipating reductants in the plastid; under nitrate-limiting conditions, sulfate assimilation plays a similar role. The use of either nitrate or sulfate uptake to balance redox reactions leads to the secretion of distinct organic nitrogen and sulfur compounds. Such compounds can be accessed by bacteria in the surface ocean. The model of the diatom Thalassiosira pseudonana provides a mechanistic explanation for the production of ecologically and climatologically relevant compounds that may serve as the basis for intricate, cross-kingdom microbial networks. Diatom metabolism has an important influence on global biogeochemistry; metabolic models of marine microorganisms link genes to ecosystems and may be key to integrating molecular data with models of ocean biogeochemistry.

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Cord blood genomic analysis highlights the role of redox balance.

Publications

Cord blood genomic analysis highlights the role of redox balance.

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