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Bushuev, A. V.; Aleeva, T. B.; Petrova, E. V.; Zubarev, V. N.; Nikolaev, A. G.; Семенов, В.Г.; Silin, Boris; Dmitriev, A. M.

doi:10.1023/a:1023629020300

Cited by 11 publications

(1 citation statement)

References 6 publications

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“…HIF is part of a well-understood pathway linking changes in the concentration of molecular oxygen to alterations in transcription of a broad range of genes ( 42 ). Genetic manipulation of this system in mice and a rare genetic disease (Chuvash polycythemia) that results in partial HIF activation in humans have both shown that this system plays an important role in determining a number of physiological characteristics including the erythropoietic ( 2 , 3 , 12 , 22 , 39 , 46 , 54 ), ventilatory ( 28 , 48 ), and cardiopulmonary ( 9 , 10 , 47 , 48 , 54 ) responses to hypoxia. Our hypothesis is that variations within the HIF transcription system underlie at least part of the variation in systems-level responses to hypoxia among normal human individuals.…”

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confidence: 99%

Variations within oxygen-regulated gene expression in humans

Brooks¹,

Elvidge²,

Glenny³

et al. 2009

Journal of Applied Physiology

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The effects of hypoxia on gene transcription are mainly mediated by a transcription factor complex termed hypoxia-inducible factor (HIF). Genetic manipulation of animals and studies of humans with rare hereditary disease have shown that modifying the HIF pathway affects systems-level physiological responses to hypoxia. It is, however, an open question whether variations in systems-level responses to hypoxia between individuals could arise from variations within the HIF system. This study sought to determine whether variations in the responsiveness of the HIF system at the cellular level could be detected between normal individuals. Peripheral blood lymphocytes (PBL) were isolated on three separate occasions from each of 10 healthy volunteers. After exposure of PBL to eight different oxygen tensions ranging from 20% to 0.1%, the expression levels of four HIF-regulated transcripts involved in different biological pathways were measured. The profile of expression of all four transcripts in PBL was related to oxygen tension in a curvilinear manner. Double logarithmic transformation of these data resulted in a linear relationship that allowed the response to be parameterized through a gradient and intercept. Analysis of variance (ANOVA) on these parameters showed that the level of between-subject variation in the gradients of the responses that was common across all four HIF-regulated transcripts was significant (P = 0.008). We conclude that statistically significant variation within the cellular response to hypoxia can be detected between normal humans. The common nature of the variability across all four HIF-regulated genes suggests that the source of this variation resides within the HIF system itself.

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