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Article

Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”

1
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy
2
Council for Agricultural Research and Economics—Food and Nutrition Research Centre (C.R.E.A.-AN), 00198 Rome, Italy
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Environmental, Occupational, Ageing (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1180 Brussels, Belgium
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Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles, 1050 Brussels, Belgium
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Department of Anaesthesiology, Erasme University Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium
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Hyperbaric Centre, Queen Astrid Military Hospital, 1120 Brussels, Belgium
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Motor Sciences Department, Physical Activity Teaching Unit, Université Libre de Bruxelles, 1050 Brussels, Belgium
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 458; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010458
Received: 30 November 2020 / Revised: 31 December 2020 / Accepted: 1 January 2021 / Published: 5 January 2021
(This article belongs to the Special Issue Cellular Oxygen Homeostasis)
The term “normobaric oxygen paradox” (NOP), describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as oxygen shortage, and resulting in up-regulation of the Hypoxia-inducible factor 1α (HIF-1α) transcription factor activity. The molecular characteristics of this response have not been yet fully characterized. Herein, we report the activation time trend of oxygen-sensitive transcription factors in human peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects after one hour of exposure to mild (MH), high (HH) and very high (VHH) hyperoxia, corresponding to 30%, 100%, 140% O2, respectively. Our observations confirm that MH is perceived as a hypoxic stress, characterized by the activation of HIF-1α and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), but not Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Conversely, HH is associated to a progressive loss of NOP response and to an increase in oxidative stress leading to NRF2 and NF-kB activation, accompanied by the synthesis of glutathione (GSH). After VHH, HIF-1α activation is totally absent and oxidative stress response, accompanied by NF-κB activation, is prevalent. Intracellular GSH and Matrix metallopeptidase 9 (MMP-9) plasma levels parallel the transcription factors activation pattern and remain elevated throughout the observation time. In conclusion, our study confirms that, in vivo, the return to normoxia after MH is sensed as a hypoxic trigger characterized by HIF-1α activation. On the contrary, HH and VHH induce a shift toward an oxidative stress response, characterized by NRF2 and NF-κB activation in the first 24 h post exposure. View Full-Text
Keywords: pulsed hyperoxia; HIF-1α; NRF2; NF-κB; hyperbaric oxygen; relative hypoxia pulsed hyperoxia; HIF-1α; NRF2; NF-κB; hyperbaric oxygen; relative hypoxia
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MDPI and ACS Style

Fratantonio, D.; Virgili, F.; Zucchi, A.; Lambrechts, K.; Latronico, T.; Lafère, P.; Germonpré, P.; Balestra, C. Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”. Int. J. Mol. Sci. 2021, 22, 458. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010458

AMA Style

Fratantonio D, Virgili F, Zucchi A, Lambrechts K, Latronico T, Lafère P, Germonpré P, Balestra C. Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”. International Journal of Molecular Sciences. 2021; 22(1):458. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010458

Chicago/Turabian Style

Fratantonio, Deborah, Fabio Virgili, Alessandro Zucchi, Kate Lambrechts, Tiziana Latronico, Pierre Lafère, Peter Germonpré, and Costantino Balestra. 2021. "Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”" International Journal of Molecular Sciences 22, no. 1: 458. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010458

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