Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”
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...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/458 |
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| author | Deborah Fratantonio Fabio Virgili Alessandro Zucchi Kate Lambrechts Tiziana Latronico Pierre Lafère Peter Germonpré Costantino Balestra |
| author_facet | Deborah Fratantonio Fabio Virgili Alessandro Zucchi Kate Lambrechts Tiziana Latronico Pierre Lafère Peter Germonpré Costantino Balestra |
| author_sort | Deborah Fratantonio |
| collection | DOAJ |
| description | 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% O<sub>2</sub>, 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:28:39Z |
| publishDate | 2021-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-06234fde415047cfb2fdd0f2a187a27e2023-11-21T08:29:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122145810.3390/ijms22010458Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”Deborah Fratantonio0Fabio Virgili1Alessandro Zucchi2Kate Lambrechts3Tiziana Latronico4Pierre Lafère5Peter Germonpré6Costantino Balestra7Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, ItalyCouncil for Agricultural Research and Economics—Food and Nutrition Research Centre (C.R.E.A.-AN), 00198 Rome, ItalyEnvironmental, Occupational, Ageing (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1180 Brussels, BelgiumEnvironmental, Occupational, Ageing (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1180 Brussels, BelgiumDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, ItalyEnvironmental, Occupational, Ageing (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1180 Brussels, BelgiumCouncil for Agricultural Research and Economics—Food and Nutrition Research Centre (C.R.E.A.-AN), 00198 Rome, ItalyEnvironmental, Occupational, Ageing (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1180 Brussels, BelgiumThe 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% O<sub>2</sub>, 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.https://www.mdpi.com/1422-0067/22/1/458pulsed hyperoxiaHIF-1αNRF2NF-κBhyperbaric oxygenrelative hypoxia |
| spellingShingle | Deborah Fratantonio Fabio Virgili Alessandro Zucchi Kate Lambrechts Tiziana Latronico Pierre Lafère Peter Germonpré Costantino Balestra 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 pulsed hyperoxia HIF-1α NRF2 NF-κB hyperbaric oxygen relative hypoxia |
| title | Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_full | Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_fullStr | Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_full_unstemmed | Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_short | Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_sort | increasing oxygen partial pressures induce a distinct transcriptional response in human pbmc a pilot study on the normobaric oxygen paradox |
| topic | pulsed hyperoxia HIF-1α NRF2 NF-κB hyperbaric oxygen relative hypoxia |
| url | https://www.mdpi.com/1422-0067/22/1/458 |
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