Malorni W, Iosi F, Santini M T, Testa U
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
J Cell Sci. 1993 Sep;106 ( Pt 1):309-18. doi: 10.1242/jcs.106.1.309.
It has been demonstrated that perturbation of oxidative balance plays an important role in numerous pathological states as well as in physiological modifications leading to aging. In order to evaluate the role of the oxidative state in cells, biochemical and ultrastructural studies were carried out on K562 and HL-60 cell cultures. Particular attention was given to the transferrin receptor, which plays an important role in cellular iron metabolism. In order to evaluate if oxidative stress influences the transferrin receptor regulation process, the free-radical inducer menadione was used. The results obtained seem to indicate that oxidative stress is capable of inducing a rapid and specific down-modulation of the membrane transferrin receptor due to a block of receptor recycling on the cell surface, without affecting ligand-binding affinity. These effects were observed in the early stages of menadione treatment and before any typical signs of subcellular damage, including surface blebbing, a well-known cytopathological marker of menadione-induced injury. The mechanisms underlying such phenomena appear to be related to cytoskeletal protein thiol group oxidation as well as to the perturbation of calcium homeostasis, both induced by menadione. It is thus hypothesized that the data reported here represent a specific example of a general mechanism by which cell surface receptor expression and recycling can be influenced by oxidative balance.
业已证明，氧化平衡的扰动在众多病理状态以及导致衰老的生理变化中起着重要作用。为了评估氧化状态在细胞中的作用，对K562和HL-60细胞培养物进行了生化和超微结构研究。特别关注了转铁蛋白受体，其在细胞铁代谢中起重要作用。为了评估氧化应激是否影响转铁蛋白受体的调节过程，使用了自由基诱导剂甲萘醌。所得结果似乎表明，氧化应激能够由于细胞表面受体再循环受阻而诱导膜转铁蛋白受体快速且特异性地下调，而不影响配体结合亲和力。这些效应在甲萘醌处理的早期阶段以及在任何亚细胞损伤的典型迹象（包括表面起泡，这是甲萘醌诱导损伤的众所周知的细胞病理学标志物）出现之前就已观察到。此类现象背后的机制似乎与甲萘醌诱导的细胞骨架蛋白硫醇基团氧化以及钙稳态的扰动有关。因此推测，此处报道的数据代表了一种普遍机制的具体实例，即氧化平衡可影响细胞表面受体的表达和再循环。
