Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides
Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides
复制标题
DOI：
10.1016/j.bbrc.2005.03.146
复制
发表时间：
2005-05-27
影响因子：
3.1
通讯作者：
Fujii, J
中科院分区：
文献类型：
--
作者：
Nagaoka, Y;Otsu, K;Fujii, J
在光动力化疗中，单线态氧是光诱导皮肤光老化和肿瘤细胞毒性过程的原因之一。为了更好地理解单线态氧修饰蛋白质的功能后果，萘内过氧物对溶酶体蛋白水解酶的影响。对组织蛋白酶进行了检测。正常胎儿皮肤成纤维细胞的可溶性部分经过氧化处理后，半胱氨酸蛋白酶(组织蛋白酶B和L/S)的活性受到抑制，而天冬氨酸蛋白酶(组织蛋白酶D/E)的活性不受抑制。用二硫苏糖醇处理内过氧化处理的可溶性组分，几乎不能恢复活性。组织蛋白酶B是从正常人肝脏中提纯的，与胞浆中的组织蛋白酶B相似。这些数据表明，单线态氧氧化修饰了催化所必需的氨基酸残基，从而导致半胱氨酸蛋白酶类型组织蛋白酶的不可逆失活。(C)2005 Elsevier Inc.保留所有权利。
Singlet oxygen is a causal factor in light-induced skin photoaging and the cytotoxic process Of tumor cells in photodynamic chemotherapy. To develop a better understanding of the functional consequences of protein modification by singlet oxygen, the effects of naphthalene endoperoxide on lysosomal protease. cathepsin, were examined. When the soluble fraction of normal human fetal skin fibroblast cells was treated with the endoperoxide, the activities of cysteine proteases, cathepsins B and L/S, were inhibited, but that of aspartate protease, cathepsin D/E. was not. The reduction of the endoperoxide-treated soluble fractions by treatment with dithiothreitol barely recovered the activities. Cathepsin B, purified from normal human liver, exhibited similar profiles to that in cytosol. These data suggest that singlet oxygen oxidatively modifies an amino acid residue essential for catalysis and consequently results in the irreversible inactivation of cysteine protease-type cathepsin. (c) 2005 Elsevier Inc. All rights reserved.