Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox”
The “normobaric oxygen paradox” (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in h...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/4/2394 |
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| author | Costantino Balestra Sara Baldelli Fabio Virgili Michele Salvagno Simona Mrakic-Sposta Deborah Fratantonio |
| author_facet | Costantino Balestra Sara Baldelli Fabio Virgili Michele Salvagno Simona Mrakic-Sposta Deborah Fratantonio |
| author_sort | Costantino Balestra |
| collection | DOAJ |
| description | The “normobaric oxygen paradox” (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O<sub>2</sub>), and high hyperoxia, HH (100% O<sub>2</sub>), while during very high hyperoxia, VHH (140% O<sub>2</sub>), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-07T22:28:21Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-20d9a65975ae46698f3de19f6683779d2024-02-23T15:20:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254239410.3390/ijms25042394Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox”Costantino Balestra0Sara Baldelli1Fabio Virgili2Michele Salvagno3Simona Mrakic-Sposta4Deborah Fratantonio5Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, BelgiumDepartment of Human Sciences and Promotion of the Quality of Life, IRCCS San Raffaele Pisana, San Raffaele Roma Open University, 00163 Rome, ItalyInteruniversitary Consortium “National Institute for Bio-Structures and Bio-Systems”—I.N.B.B., 13, 00136 Rome, ItalyDepartment of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), 1070 Brussels, BelgiumInstitute of Clinical Physiology, National Research Council (CNR), 20162 Milan, ItalyDepartment of Medicine and Surgery, LUM University, S.S. 100 Km 18, 70100 Casamassima, ItalyThe “normobaric oxygen paradox” (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O<sub>2</sub>), and high hyperoxia, HH (100% O<sub>2</sub>), while during very high hyperoxia, VHH (140% O<sub>2</sub>), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism.https://www.mdpi.com/1422-0067/25/4/2394humanperipheral blood mononuclear cells (PBMCs)reactive oxygen species (ROS)oxidative stressNrf2PGC-1α |
| spellingShingle | Costantino Balestra Sara Baldelli Fabio Virgili Michele Salvagno Simona Mrakic-Sposta Deborah Fratantonio Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” International Journal of Molecular Sciences human peripheral blood mononuclear cells (PBMCs) reactive oxygen species (ROS) oxidative stress Nrf2 PGC-1α |
| title | Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_full | Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_fullStr | Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_full_unstemmed | Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_short | Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the “Normobaric Oxygen Paradox” |
| title_sort | pulsed hyperoxia acts on plasmatic advanced glycation end products and advanced oxidation protein products and modulates mitochondrial biogenesis in human peripheral blood mononuclear cells a pilot study on the normobaric oxygen paradox |
| topic | human peripheral blood mononuclear cells (PBMCs) reactive oxygen species (ROS) oxidative stress Nrf2 PGC-1α |
| url | https://www.mdpi.com/1422-0067/25/4/2394 |
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