Stridsberg Mats, Eriksson Barbro, Oberg Kjell, Janson Eva Tiensuu
Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, S-751 85, Uppsala, Sweden.
Regul Pept. 2004 Mar 15;117(3):219-27. doi: 10.1016/j.regpep.2003.10.023.
The primary structure of human chromogranin A (CgA) not only contains 10 pairs of basic amino acids, which are potential cleavage sites for specific endogenous proteases, but also other sites in the molecule can be subjected to cleavage. Several CgA-related peptides have been identified in tissue, and many of the biological effects attributed to CgA seem to be mediated by these peptides.
Peptides homologous to defined parts of the human CgA molecule were selected and synthesised. Antibodies were raised, and 11 specific radioimmunoassays were developed. Plasma samples from 20 patients with neuroendocrine tumours were collected and measured in all assays.
All assays measured circulating levels of CgA-derived peptides. Only four of the assays measured concentrations that correlated with that of total CgA. However, concentrations of the individual CgA-related peptides were generally lower than the concentration of total CgA. Different neuroendocrine tumours seem to process CgA differently. The ratio between a given region-specific assay and total CgA is inversely correlated to tumour activity.
The assays presented allow measurements of defined regions of CgA and will thus become important tools for further studies of processing of CgA.
人嗜铬粒蛋白A（CgA）的一级结构不仅含有10对碱性氨基酸，这些是特定内源性蛋白酶的潜在切割位点，而且分子中的其他位点也可被切割。已在组织中鉴定出几种与CgA相关的肽，许多归因于CgA的生物学效应似乎是由这些肽介导的。
选择并合成了与人CgA分子特定部分同源的肽。制备了抗体，并开发了11种特异性放射免疫分析方法。收集了20例神经内分泌肿瘤患者的血浆样本，并在所有分析中进行检测。
所有分析均测量了CgA衍生肽的循环水平。只有四种分析测量的浓度与总CgA浓度相关。然而，各个与CgA相关的肽的浓度通常低于总CgA的浓度。不同的神经内分泌肿瘤似乎对CgA的处理方式不同。给定区域特异性分析与总CgA之间的比率与肿瘤活性呈负相关。
所提供的分析方法能够测量CgA的特定区域，因此将成为进一步研究CgA加工过程的重要工具。
