Investigating the effects of hyperbaric oxygen on mitochondrial function of endothelial progenitor cells.

Abstract

Hyperbaric oxygen treatment (HBOT) is a FDA approved adjunctive therapy for 14 different conditions, including delayed radiation injury, impaired wound healing, compromised skin grafts and compression sickness. Patients typically receive multiple daily treatments in chambers pressurized up to 3.0 atmospheres with 100% oxygen, depending on the disease state/type. We previously demonstrated that HBOT stimulates vasculogenic stem cell growth and differentiation in vivo, by creating a physiological redox‐active autocrine loop in circulating progenitor cells. Recent studies also supported the role of HBOT in activation of redox‐regulated pathways including hypoxia inducible factor (HIF), mitogen‐activated protein kinase (MAPK), thioredoxin (Trx) system, nuclear factor erythroid 2 (Nrf2) as well as nitric oxide (NO) signaling. In this study we proposed that alterations in mitochondrial function is an early event following HBOT. Mice were treated with HBO for 90 min at 2.8 ATA. Cellular bioenergetics and mitochondrial respiration were assessed immediately following treatment in primary cells using Seahorse Extracellular flux analyzer. Oxygen consumption rate (OCR) was measured after the sequential injections of oligomycin (inhibitor of ATP synthase), carbonyl cyanide p‐trifluoromethoxyphenylhydrazone (FCCP; uncoupler of mitochondrial inner membrane), and antimycin A (inhibitor of complex III). HBOT significantly altered the basal respiration as well as spare respiratory capacity. Furthermore, the mitochondrial mass is significantly increased following a single HBOT session. Future studies will determine the effect of multiple HBOT sessions on mitochondrial function and cellular bioenergetics, which can provide novel targets to improve the efficacy of an already safe and approved therapy.Support or Funding InformationThis project is funded by NIGMS, Center of Biomedical Research Excellence Award, P20GM109005