Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells
Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells
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DOI：
10.1074/jbc.m102630200
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发表时间：
2001-07-06
影响因子：
4.8
通讯作者：
Yoshizato, K
中科院分区：
文献类型：
--
作者：
Kawada, N;Kristensen, DB;Yoshizato, K
利用蛋白质组学方法对大鼠肝星状细胞（一种肝特异性周细胞）的活化进行分子分析，发现了一种新的蛋白质STAP（星状细胞活化相关蛋白）。我们克隆了STAP cDNA，STAP是一种分子量为21，496的胞质蛋白，与肌红蛋白的氨基酸序列同源性约为40%，STAP在从纤维化肝分离的体内活化的星状细胞和在原代培养期间经历体外活化的星状细胞中显著诱导。这种诱导与其他活化相关分子如平滑肌α-肌动蛋白、PDGF受体β和神经细胞粘附分子的诱导一起观察到。在硫代乙酰胺诱导的肝纤维化中，STAP蛋白和mRNA的表达呈时间依赖性增加。免疫电子显微镜和蛋白质组分析检测STAP在星状细胞，但没有在其他肝组成细胞。重组大鼠STAP的生化特性表明，STAP是一个血红素蛋白表现出对过氧化氢和亚油酸氢过氧化物酶活性。这些结果表明，STAP是一种新的内源性过氧化物酶，分解代谢过氧化氢和脂质过氧化氢，这两者都已被报道触发星状细胞活化，从而促进肝纤维化的进展，因此STAP可能在肝脏中发挥抗纤维化的过氧化物清除剂的作用。
A proteome approach for the molecular analysis of the activation of rat stellate cell, a liver-specific pericyte, led to the discovery of a novel protein named STAP (stellate cell activation-associated protein). We cloned STAP cDNA, STAP is a cytoplasmic protein with molecular weight of 21,496 and shows about 40% amino acid sequence homology with myoglobin, STAP was dramatically induced in in vivo activated stellate cells isolated from fibrotic liver and in stellate cells undergoing in vitro activation during primary culture. This induction was seen together with that of other activation-associated molecules, such as smooth muscle alpha -actin, PDGF receptor-beta, and neural cell adhesion molecule. The expression of STAP protein and mRNA was augmented time dependently in thioacetamide-induced fibrotic liver. Immunoelectron microscopy and proteome analysis detected STAP in stellate cells but not in other hepatic constituent cells. Biochemical characterization of recombinant rat STAP revealed that STAP is a heme protein exhibiting peroxidase activity toward hydrogen peroxide and linoleic acid hydroperoxide. These results indicate that STAP is a novel endogenous peroxidase catabolizing hydrogen peroxide and lipid hydroperoxides, both of which have been reported to trigger stellate cell activation and consequently promote progression of liver fibrosis, STAP could thus play a role as an antifibrotic scavenger of peroxides in the liver.