Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia
Marine mammals tolerate repeated bouts of hypoxemia while diving, with up to 90% of blood oxygen stores depleted in some species. Accordingly, tissues such as the endothelium experience acute fluctuations in oxygen availability. In terrestrial mammals, hypoxia/reoxygenation events of similar magnitu...
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crwiley:10.1096/fasebj.2020.34.s1.04299 2024-06-02T08:06:03+00:00 Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia Allen, Kaitlin Vázquez-Medina, José Pablo 2020 http://dx.doi.org/10.1096/fasebj.2020.34.s1.04299 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor The FASEB Journal volume 34, issue S1, page 1-1 ISSN 0892-6638 1530-6860 journal-article 2020 crwiley https://doi.org/10.1096/fasebj.2020.34.s1.04299 2024-05-03T11:29:43Z Marine mammals tolerate repeated bouts of hypoxemia while diving, with up to 90% of blood oxygen stores depleted in some species. Accordingly, tissues such as the endothelium experience acute fluctuations in oxygen availability. In terrestrial mammals, hypoxia/reoxygenation events of similar magnitude contribute to inflammatory signaling, reactive oxygen species (ROS) generation, and endothelial dysfunction in pathological settings. Marine mammals, however, appear well protected against oxidant stress and inflammation despite repeated exposure to hypoxia/reoxygenation, though the specific cellular mechanisms driving this protection remain unknown. We isolated endothelial cells (ECs) from placental arteries from northern elephant seals ( Mirounga angustirostris ), a pinniped species noted for its extreme diving capacity. Seal primary EC cultures proliferate, express the canonical EC markers PECAM‐1 and VE‐cadherin, and take up acetylated LDL. Seal ECs are metabolically active in adherent culture and respond to mitochondrial inhibition and uncoupling and pharmacological NADPH oxidase activation, demonstrating utility as a live, functionally relevant system in which to study the biochemical drivers of hypoxia/reoxygenation tolerance in diving seals. Seal ECs exposed to 1% O 2 for up to 6 hours upregulated HIF‐1α protein, with maximal expression occurring within 15 minutes (68‐fold increase over normoxic levels). Human ECs matched this magnitude (73‐fold increase) though not until 1 hour, after which expression of HIF‐1α rapidly and progressively declined (22‐fold above normoxic levels at 6 hours). In contrast, seal ECs maintained elevated HIF‐1α protein expression (52‐fold) at 6 hours. Pharmacological stimulation with menadione, an inducer of redox cycling, significantly increased oxidant generation in human (5‐fold, p=0.027) but not seal ECs (2.5‐fold, p=0.18), as did acute exposure to hypoxia/reoxygenation . Together, our data show that seal ECs mount a rapid, sustained response to hypoxia /reoxygenation events, ... Article in Journal/Newspaper Elephant Seals Wiley Online Library The FASEB Journal 34 S1 1 1 |
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Wiley Online Library |
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English |
description |
Marine mammals tolerate repeated bouts of hypoxemia while diving, with up to 90% of blood oxygen stores depleted in some species. Accordingly, tissues such as the endothelium experience acute fluctuations in oxygen availability. In terrestrial mammals, hypoxia/reoxygenation events of similar magnitude contribute to inflammatory signaling, reactive oxygen species (ROS) generation, and endothelial dysfunction in pathological settings. Marine mammals, however, appear well protected against oxidant stress and inflammation despite repeated exposure to hypoxia/reoxygenation, though the specific cellular mechanisms driving this protection remain unknown. We isolated endothelial cells (ECs) from placental arteries from northern elephant seals ( Mirounga angustirostris ), a pinniped species noted for its extreme diving capacity. Seal primary EC cultures proliferate, express the canonical EC markers PECAM‐1 and VE‐cadherin, and take up acetylated LDL. Seal ECs are metabolically active in adherent culture and respond to mitochondrial inhibition and uncoupling and pharmacological NADPH oxidase activation, demonstrating utility as a live, functionally relevant system in which to study the biochemical drivers of hypoxia/reoxygenation tolerance in diving seals. Seal ECs exposed to 1% O 2 for up to 6 hours upregulated HIF‐1α protein, with maximal expression occurring within 15 minutes (68‐fold increase over normoxic levels). Human ECs matched this magnitude (73‐fold increase) though not until 1 hour, after which expression of HIF‐1α rapidly and progressively declined (22‐fold above normoxic levels at 6 hours). In contrast, seal ECs maintained elevated HIF‐1α protein expression (52‐fold) at 6 hours. Pharmacological stimulation with menadione, an inducer of redox cycling, significantly increased oxidant generation in human (5‐fold, p=0.027) but not seal ECs (2.5‐fold, p=0.18), as did acute exposure to hypoxia/reoxygenation . Together, our data show that seal ECs mount a rapid, sustained response to hypoxia /reoxygenation events, ... |
format |
Article in Journal/Newspaper |
author |
Allen, Kaitlin Vázquez-Medina, José Pablo |
spellingShingle |
Allen, Kaitlin Vázquez-Medina, José Pablo Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
author_facet |
Allen, Kaitlin Vázquez-Medina, José Pablo |
author_sort |
Allen, Kaitlin |
title |
Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
title_short |
Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
title_full |
Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
title_fullStr |
Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
title_full_unstemmed |
Primary Endothelial Cells from Seals Mount a Rapid and Sustained Response to Acute Hypoxia |
title_sort |
primary endothelial cells from seals mount a rapid and sustained response to acute hypoxia |
publisher |
Wiley |
publishDate |
2020 |
url |
http://dx.doi.org/10.1096/fasebj.2020.34.s1.04299 |
genre |
Elephant Seals |
genre_facet |
Elephant Seals |
op_source |
The FASEB Journal volume 34, issue S1, page 1-1 ISSN 0892-6638 1530-6860 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1096/fasebj.2020.34.s1.04299 |
container_title |
The FASEB Journal |
container_volume |
34 |
container_issue |
S1 |
container_start_page |
1 |
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1 |
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1800750927310749696 |