Abstract
Enucleated mature human erythrocytes possess NFĸBs and their upstream kinases. There is a negative correlation between eryptosis (cell death of erythrocytes) and the amount of NFĸB subunits p50 and Rel A (p65). This finding is based on the fact that young erythrocytes have the highest levels of NFĸBs and the lowest eryptosis rate, while in old erythrocytes the opposite ratio prevails. Human erythrocytes (hRBCs) effectively control the homeostasis of the cell membrane permeable anti-inflammatory signal molecule hydrogen sulfide (H(2)S). They endogenously produce H(2)S via both non-enzymic (glutathione-dependent) and enzymic processes (mercaptopyruvate sulfur transferase-dependent). They uptake H(2)S from diverse tissues and very effectively degrade H(2)S via methemoglobin (Hb-Fe(3+))-catalyzed oxidation. Interestingly, a reciprocal correlation exists between the intensity of inflammatory diseases and endogenous levels of H(2)S. H(2)S deficiency has been observed in patients with diabetes, psoriasis, obesity, and chronic kidney disease (CKD). Furthermore, endogenous H(2)S deficiency results in impaired renal erythropoietin (EPO) production and EPO-dependent erythropoiesis. In general we can say: dynamic reciprocal interaction between tumor suppressor and oncoproteins, orchestrated and sequential activation of pro-inflammatory NFĸB heterodimers (RelA-p50) and the anti-inflammatory NFĸB-p50 homodimers for optimal inflammation response, appropriate generation, subsequent degradation of H(2)S etc., are prerequisites for a functioning cell and organism. Diseases arise when the fragile balance between different signaling pathways that keep each other in check is permanently disturbed. This work deals with the intact anti-inflammatory hRBCs and their role as guarantors to maintain the redox status in the physiological range, a basis for general health and well-being.