Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

• DOI: 10.1016/j.redox.2022.102535
• Publication Date: 2022-11-16T06:55:10Z
• Authors: Simone Fenk; Elizaveta V. Meln...; Anastasia A. Anas...; Yuri M. Poluektov; Pavel I. Zaripov; Vladimir A. Mitke...; Yaroslav V. Tkachev; Lars Kaestner; Giampaolo Minetti; Heimo Mairbäurl; Jeroen S. Goede; Alexander A. Makarov; Irina Yu Petrushanko; Anna Bogdanova
• Keywords: Deoxygenation; Isothermal Titration Calorimetry; Methemoglobin

Fast changes in environmental oxygen availability translate into shifts mitochondrial free radical production. An increase intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released circulation from hypoxic peripheral tissues. Although reported, mechanism behind this acute oxygen-dependent regulation GSH red blood cells remains unknown. This study explores role hemoglobin (Hb) modulation levels cells. We have demonstrated that a decrease Hb O2 saturation to 50% or less observed healthy humans while at high altitude, cell suspensions results rising level is proportional reduction saturation. effect was not caused by stimulation de novo synthesis its release deglutathionylation Hb's cysteines. Using isothermal titration calorimetry and silico modeling, we non-covalent binding four molecules oxy-Hb two them upon deoxygenation. Localization sites within molecule identified. Oxygen-dependent occurred reciprocally 2,3-bisphosphoglycerate. Furthermore, noncovalent moderately increased affinity. Taken together, our findings identified an adaptive which may provide advanced antioxidant defense respond oxidative challenges immediately