Cox S W, Eley B M
Department of Periodontology, King's College School of Medicine and Dentistry, London, England, U.K.
Arch Oral Biol. 1987;32(9):599-605. doi: 10.1016/0003-9969(87)90031-8.
The cysteine proteinases cathepsins B and L have collagenolytic potential and so have been implicated in connective-tissue breakdown in chronic periodontitis. Synthetic peptide substrates are often used to detect proteolytic enzymes. The action of homogenates of inflamed gingiva tissue against three such substrates of cathepsin B have been characterized here by protease inhibitors. Using the selective reagents ZPheAlaCHN2, BzValLysLysArgAFC, ZAlaArgArgAFC and ZPheArgAFC were susceptible to both cysteine and non-cysteine proteinase activity; the two types of enzymes had acidic and alkaline pH optima, respectively. The action of other inhibitors at acidic pH indicated the involvement of cathepsin B and, to a lesser extent, cathepsin L. The enzyme active at alkaline pH was a serine proteinase; it resembled glandular kallikrein in its inhibitor response and its ability to hydrolyse a fourth substrate, DValLeuArgAFC, but its greater reactivity with BzValLysLysArgAFC and ZAlaArgArgAFC was not consistent with kallikrein. ZPheArgAFC, though less sensitive than BzValLysLysArgAFC to cysteine proteinase action, was far less susceptible to hydrolysis by the serine proteinase and thus appears the best choice for selective assays of cathepsins B and L.
半胱氨酸蛋白酶组织蛋白酶B和L具有胶原溶解潜能,因此被认为与慢性牙周炎中结缔组织的破坏有关。合成肽底物常被用于检测蛋白水解酶。在此,通过蛋白酶抑制剂对炎症牙龈组织匀浆作用于组织蛋白酶B的三种此类底物的情况进行了表征。使用选择性试剂时,ZPheAlaCHN2、BzValLysLysArgAFC、ZAlaArgArgAFC和ZPheArgAFC对半胱氨酸和非半胱氨酸蛋白酶活性均敏感;这两种类型的酶的最适pH值分别为酸性和碱性。其他抑制剂在酸性pH下的作用表明组织蛋白酶B参与其中,组织蛋白酶L的参与程度较小。在碱性pH下具有活性的酶是一种丝氨酸蛋白酶;它在抑制剂反应及其水解第四种底物DValLeuArgAFC的能力方面类似于腺体激肽释放酶,但其与BzValLysLysArgAFC和ZAlaArgArgAFC的更高反应性与激肽释放酶不一致。ZPheArgAFC虽然对半胱氨酸蛋白酶作用的敏感性低于BzValLysLysArgAFC,但对丝氨酸蛋白酶水解的敏感性要低得多,因此似乎是组织蛋白酶B和L选择性测定的最佳选择。