Hydrogen peroxide diffusion across the red blood cell membrane occurs mainly by simple diffusion through the lipid fraction.

Hydrogen peroxide (H ₂ O ₂ ) is an oxidant produced endogenously by several enzymatic pathways. While it can cause molecular damage, H ₂ O ₂ also plays a role in regulating cell proliferation and survival through redox signaling pathways. In the vascular system, red blood cells (RBCs) are notably efficient at metabolizing H ₂ O ₂ . In addition to a robust antioxidant defense, we recently determined that human RBCs also have a high membrane permeability to H ₂ O ₂ that is independent of aquaporin 1 or aquaporin 3. In this work, we sought to further investigate the permeation mechanism of H ₂ O ₂ through the membrane of human RBCs. First, we explored the role of other erythrocytic membrane proteins in H ₂ O ₂ transport, including urea transporter B and ammonia transporter Rh proteins. However, no differences were found in H ₂ O ₂ permeability in RBCs lacking these proteins compared to control RBCs. We then focused on the hypothesis that H ₂ O ₂ diffuses through the lipid bilayer. To test this, we studied H ₂ O ₂ permeability in RBCs from patients with Gaucher disease (GD), which accumulate sphingolipids in the membrane, affecting RBC morphology and deformability. We found that RBCs from GD patients exhibited lower H₂O₂ membrane permeability. In another approach, we treated normal RBCs with hexanol, which fluidizes the lipid fraction of the RBC membrane, and observed an increase in the permeability to H ₂ O ₂ . In contrast, hexanol had no effect on the rate of water efflux by aquaporin 1. Together, these results support the hypothesis that H ₂ O ₂ diffusion through the RBC membrane occurs primarily through the lipid fraction.
Competing Interests: Declarations of interest None.
(Copyright © 2024 Elsevier Inc. All rights reserved.)