Abstract
The primary role for erythrocytes is oxygen transport that requires the reversible binding of oxygen to hemoglobin. There are, however, secondary reactions whereby the erythrocyte can generate reactive oxygen species (ROS) and nitric oxide (NO). ROS such as superoxide anion and hydrogen peroxide are generated by the autoxidation of hemoglobin. NO can be generated when nitrite reacts with hemoglobin forming an HbNO+ intermediate. Both of these reactions are dramatically enhanced under hypoxic conditions. Within the erythrocyte, interactions of NO with hemoglobin and enzymatic reactions that neutralize ROS are expected to prevent the release of any generated NO or ROS. We have, however, demonstrated that partially oxygenated hemoglobin has a distinct conformation that enhances hemoglobin-membrane interactions involving Band 3 protein. Autoxidation of the membrane bound partially oxygenated hemoglobin facilitates the release of ROS from the erythrocyte. NO release is made possible when HbNO+, the hemoglobin nitrite-reduced intermediate, which is not neutralized by hemoglobin, is bound to the membrane and releases NO. Some of the released ROS has been shown to be transferred to the vasculature suggesting that some of the released NO may also be transferred to the vasculature. NO is known to have a major effect on the vasculature regulating vascular dilatation. Erythrocyte generated NO may be important when NO production by the vasculature is impaired. Furthermore, the erythrocyte NO released, may play an important role in regulating vascular function under hypoxic conditions when endothelial eNOS is less active. ROS can react with NO and, can thereby modulate the vascular effects of NO. We have also demonstrated an inflammatory response due to erythrocyte ROS. This reflects the ability of ROS to react with various cellular components affecting cellular function.
Highlights
The primary role of the erythrocyte is the transport of oxygen through the circulatory system and the delivery of oxygen to the tissues
A completely new perspective in our understanding of interactions between erythrocytes and the vasculature is provided by these studies
A distinct conformation of hemoglobin under hypoxic conditions provides a mechanism for the release of nitric oxide (NO) and reactive oxygen species (ROS) from the erythrocytes (Figure 3)
Summary
The primary role of the erythrocyte is the transport of oxygen through the circulatory system and the delivery of oxygen to the tissues. Found that the reaction of nitrite with deoxyhemoglobin produces two hemoglobin associated intermediates prior to the formation of NO (Salgado et al, 2009) The same conformational change for partially liganded hemoglobin that enhances the binding of partially oxygenated hemoglobin to the membrane facilitating the release of superoxide (ROS) increases the affinity of the nitrite-reacted hemoglobin for band 3 on the erythrocyte membrane and enhances the formation of NO from one of these nitrite-reacted hemoglobin intermediates (Salgado et al, 2015). Once released from the erythrocyte, possible effects of ROS and NO on the vasculature and other cells in the circulation need to be considered
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
