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 (H₂S). They endogenously produce H₂S via both non-enzymic (glutathione-dependent) and enzymic processes (mercaptopyruvate sulfur transferase-dependent). They uptake H₂S from diverse tissues and very effectively degrade H₂S via methemoglobin (Hb-Fe³⁺)-catalyzed oxidation. Interestingly, a reciprocal correlation exists between the intensity of inflammatory diseases and endogenous levels of H₂S. H₂S deficiency has been observed in patients with diabetes, psoriasis, obesity, and chronic kidney disease (CKD). Furthermore, endogenous H₂S 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 H₂S 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.

 抽象的

去核的成熟人红细胞具有 NFκB 及其上游激酶。红细胞死亡（红细胞死亡）与 NFĸB 亚基 p50 和 Rel A (p65) 的数量之间存在负相关。这一发现基于以下事实：年轻的红细胞具有最高水平的 NFκB 和最低的红细胞凋亡率，而在老年红细胞中则存在相反的比例。人红细胞（hRBC）有效控制细胞膜可渗透的抗炎信号分子硫化氢（H ₂ S）的稳态。它们通过非酶过程（依赖于谷胱甘肽）和酶过程（依赖于巯基丙酮酸硫转移酶）内源性产生H ₂ S。它们从不同的组织中吸收 H ₂ S，并通过高铁血红蛋白 (Hb-Fe ³⁺ ) 催化的氧化非常有效地降解 H ₂ S。有趣的是，炎症性疾病的强度和 H ₂ S 的内源水平之间存在相互关系。在糖尿病、牛皮癣、肥胖症和慢性肾病 (CKD) 患者中观察到 H ₂ S 缺乏。此外，内源性H ₂ S缺乏导致肾促红细胞生成素(EPO)生成和EPO依赖性红细胞生成受损。一般来说，我们可以说：肿瘤抑制因子和癌蛋白之间的动态相互作用，促炎性 NFĸB 异二聚体 (RelA-p50) 和抗炎 NFĸB-p50 同二聚体的精心策划和顺序激活，以实现最佳的炎症反应，适当的生成，随后的降解H ₂ S等是细胞和生物体发挥功能的先决条件。 当不同信号通路之间相互制约的脆弱平衡被永久破坏时，疾病就会出现。这项工作涉及完整的抗炎 hRBC 及其作为维持生理范围内氧化还原状态的保证者的作用，这是总体健康和福祉的基础。