Kell Douglas B, Pretorius Etheresia
School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, 131, Princess St, Manchester M1 7DN, Lancs, UK.
Metallomics. 2014 Apr;6(4):748-73. doi: 10.1039/c3mt00347g.
"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage.
“血清铁蛋白”存在一个悖论，因为作为铁储存蛋白的铁蛋白并非在血清中合成，却能在血清中被发现。血清铁蛋白也是一种广为人知的炎症标志物，但尚不清楚血清铁蛋白是反映炎症还是引发炎症，亦或是参与了炎症循环。我们在此认为血清铁蛋白源自受损细胞，因此是细胞损伤的标志物。血清铁蛋白中的蛋白质被认为是无害的，但它已失去（即释放出）其大部分正常的铁成分，而未结合的铁具有高度毒性。基于简单的化学动力学原理，血清铁蛋白水平与疾病以及体内铁储存量均相关这一事实是可以预期的。血清铁蛋白水平还与其他表型读数相关，如红细胞形态。总体而言，这种系统方法有助于解释血清铁蛋白的一些明显悖论，包括：（i）它为何与细胞损伤的生物标志物相关；（ii）它为何与羟基自由基形成（以及氧化应激）的生物标志物相关；（iii）因此它为何与众多疾病的存在和/或严重程度相关。这进而引出了关于如何利用血清铁蛋白水平主要代表细胞应激和损伤这一认识的推论的建议。
