Dias Wagner B, Fajardo Fernanda D, Graça-Souza Aurelio V, Freire-de-Lima Leonardo, Vieira Fabiana, Girard Murielle F, Bouteille Bernard, Previato José O, Mendonça-Previato Lucia, Todeschini Adriane R
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 22944.970, Rio de Janeiro, RJ, Brazil.
Cell Microbiol. 2008 Jan;10(1):88-99. doi: 10.1111/j.1462-5822.2007.01017.x. Epub 2007 Aug 2.
The protozoan responsible for Chagas' disease, Trypanosoma cruzi, expresses on its surface an unusual trans-sialidase enzyme thought to play an important role in host-parasite interactions. Trans-sialidase is the product of a multigene family encoding both active and inactive proteins. We have demonstrated that despite lacking enzymatic activity due to a single mutation, Tyr342-His, inactive trans-sialidase displays sialic acid binding activity, with identical specificity to that of its active analogue. In this work we demonstrate that binding of a recombinant inactive trans-sialidase to molecules containing alpha2,3-linked sialic acid on endothelial cell surface triggers NF-kappaB activation, expression of adhesion molecules and upregulation of parasite entry into host cells. Furthermore, inactive recombinant trans-sialidase blocks endothelial cell apoptosis induced by growth factor deprivation. These results suggest that inactive members of the trans-sialidase family play a role in endothelial cell responses to T. cruzi infection.
引发恰加斯病的原生动物克氏锥虫，在其表面表达一种不同寻常的转唾液酸酶，该酶被认为在宿主与寄生虫的相互作用中发挥重要作用。转唾液酸酶是一个多基因家族的产物，该家族编码有活性和无活性的蛋白质。我们已经证明，尽管由于单个突变（Tyr342-His）而缺乏酶活性，但无活性的转唾液酸酶仍表现出唾液酸结合活性，其特异性与其活性类似物相同。在这项研究中，我们证明重组无活性转唾液酸酶与内皮细胞表面含有α2,3-连接唾液酸的分子结合会触发核因子κB激活、黏附分子表达以及寄生虫进入宿主细胞的上调。此外，无活性重组转唾液酸酶可阻止因生长因子剥夺诱导的内皮细胞凋亡。这些结果表明，转唾液酸酶家族的无活性成员在内皮细胞对克氏锥虫感染的反应中发挥作用。
