CHARACTERIZATION OF AMYLOID-A PROTEIN IN HUMAN SECONDARY AMYLOIDOSIS - THE PREDOMINANT DEPOSITION OF SERUM AMYLOID-A1
CHARACTERIZATION OF AMYLOID-A PROTEIN IN HUMAN SECONDARY AMYLOIDOSIS - THE PREDOMINANT DEPOSITION OF SERUM AMYLOID-A1
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DOI：
10.1016/0925-4439(94)00076-3
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发表时间：
1995-01-25
影响因子：
6.2
通讯作者：
BENSON, MD
中科院分区：
文献类型：
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作者：
LIEPNIEKS, JJ;KLUVEBECKERMAN, B;BENSON, MD
血清淀粉样蛋白(SAA)是淀粉样蛋白(AA)的血浆前体，AA是继发性或反应性淀粉样变性淀粉样沉积中的亚单位蛋白。在人的血浆中已经发现了几种形式的急性期SAA。为了阐明这些形式的SAA是否在AA淀粉样沉积的形成中起主导作用，我们研究了6例反应性淀粉样变性患者的淀粉样蛋白亚基的氨基酸序列。当所有样品都以SAA的残基1、2或3开始时，在N端存在最小的异质性。然而，C末端的异质性更强，每种情况下AA蛋白都终止于SAA残基58到84的多个位点。由于每种情况下都不到20%的AA蛋白包含SAA残基67之后的序列，因此使用含有人类SAA1和2不同的残基52、57和60的胰蛋白酶多肽的序列和回收来确定存在的SAA1和2的相对数量。1份样品仅含有SAA1序列，4份样品含有约4个SAA1序列。11%或更少的SAA2序列，第6个含有24-33%的SAA2序列。因此，虽然六个AA样本中有五个同时含有SAA1和2，但在所有情况下，主要形式都是SAA1。在六例中的三例中，防御素蛋白与AA蛋白一起从纤维中分离出来。这可能提示中性粒细胞参与了SAA向AA纤维的转化。
Serum amyloid A protein (SAA) is the plasma precursor for amyloid A protein (AA), the subunit protein in amyloid deposits of secondary or reactive amyloidosis. Several forms of acute phase SAA have been identified in human plasma. To elucidate whether one of these forms of SAA predominates in the formation of AA amyloid deposits, the amino acid sequence of the subunit protein in six cases of reactive amyloidosis was investigated. Minimal heterogeneity was present at the N-terminus as all samples started with residue 1, 2, or 3 of SAA. The C-terminus, however, was more heterogeneous with the AA protein in each case terminating at multiple sites from residue 58 to 84 of SAA. Since less than 20% of the AA protein in each case contained sequence past residue 67 of SAA, the sequence and recovery of tryptic peptides containing residues 52, 57, and 60 where human SAA1 and 2 differ was used to determine the relative amounts of SAA1 and 2 present. One sample contained only SAA1 sequence, four contained approx. 11% or less of SAA2 sequence, and the sixth contained 24-33% of SAA2 sequence. Thus, while five of the six AA samples contained both SAA1 and 2, the predominant form in all cases was SAA1. In three of the six cases, the protein defensin was isolated along with the AA protein from the fibrils. This may suggest neutrophil involvement in SAA processing to AA fibrils.