Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals ...

• Main Authors: Allen, Kaitlin N., Torres-Velarde, Julia María, Vazquez, Juan Manuel, Moreno-Santillán, Diana D., Sudmant, Peter H., Vázquez-Medina, José Pablo
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: figshare 2024
• Subjects: Genetics; FOS: Biological sciences; Elephant Seals
• Online Access: https://dx.doi.org/10.6084/m9.figshare.c.7197263.v1; https://springernature.figshare.com/collections/Hypoxia_exposure_blunts_angiogenic_signaling_and_upregulates_the_antioxidant_system_in_endothelial_cells_derived_from_elephant_seals/7197263/1

Abstract Background Elephant seals exhibit extreme hypoxemic tolerance derived from repetitive hypoxia/reoxygenation episodes they experience during diving bouts. Real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture model from elephant seals and used RNA-seq, functional assays, and confocal microscopy to assess the molecular response to prolonged hypoxia. Results Seal and human endothelial cells exposed to 1% O2 for up to 6 h respond differently to acute and prolonged hypoxia. Seal cells decouple stabilization of the hypoxia-sensitive transcriptional regulator HIF-1α from angiogenic signaling. Rapid upregulation of genes involved in glutathione (GSH) metabolism supports the maintenance of GSH pools, and intracellular succinate increases in seal but not human cells. High maximal and spare respiratory capacity in seal cells after hypoxia ...