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A comparative study on the leishmanicidal activity of the L-amino acid oxidases BjussuLAAO-II and BmooLAAO-II isolated from Brazilian Bothrops snake venoms
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2020-11-24 , DOI: 10.1016/j.ijbiomac.2020.11.146
Luana Gonçalves Barbosa , Tássia Rafaella Costa , Isabela Pacheco Borges , Mônica Soares Costa , Anna Cecília Carneiro , Bruna Cristina Borges , Marcelo José Barbosa Silva , Fernanda Gobbi Amorim , Loïc Quinton , Kelly Aparecida Geraldo Yoneyama , Veridiana de Melo Rodrigues , Suely Vilela Sampaio , Renata Santos Rodrigues

This study aims to examine whether two L-amino acid oxidases isolated from Bothrops snake venom (SV-LAAOs) were cytotoxic to Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis, two causative agents of leishmaniasis, which is an endemic disease in tropical and subtropical countries. The SV-LAAOs BjussuLAAO-II and BmooLAAO-II were isolated from Bothrops jararacussu and Bothrops moojeni venom, respectively, through a three-step chromatography process that used molecular exclusion, hydrophobic interaction, and affinity columns. BmooLAAO-II is a new SV-LAAO isoform that we isolated in this study. The purified BjussuLAAO-II and BmooLAAO-II had high L-amino acid oxidase-specific activity: 3481.17 and 4924.77 U/mg/min, respectively. Both SV-LAAOs were strongly cytotoxic to the two Leishmania species, even at low concentrations. At the same concentration, BjussuLAAO-II and BmooLAAO-II exerted different cytotoxic effects on the parasites. We reported for the first time that the SV-LAAOs suppressed cell proliferation and altered the mitochondrial membrane potential of the two Leishmania species. Surprisingly, BjussuLAAO-II increased the intracellular reactive oxygen species production only in L. (L.) amazonensis, while BmooLAAO-II increased the intracellular reactive oxygen species production only in L. (V.) braziliensis, indicating that these SV-LAAOs had a certain specificity of action.



中文翻译:

对L-氨基酸的活性leishmanicidal的比较研究氧化酶BjussuLAAO-II和BmooLAAO-II从巴西分离矛头蛇毒

本研究旨在检验是否从分离的两种L-氨基酸氧化酶矛头蛇毒(SV-LAAOs)细胞毒性,以利什曼原虫(利什曼原虫)亚马孙利什曼原虫(Viannia)braziliensis,利什曼病两种病原体,这是一种地方性疾病在热带和亚热带国家。SV-LAAOs BjussuLAAO-II和BmooLAAO-II从Bothrops jararacussuBothrops moojeni中分离出来通过使用分子排阻,疏水相互作用和亲和柱的三步色谱法分别处理毒液。BmooLAAO-II是我们在这项研究中分离的新的SV-LAAO同工型。纯化的BjussuLAAO-II和BmooLAAO-II具有较高的L-氨基酸氧化酶比活性:分别为3481.17和4924.77 U / mg / min。两种SV-LAAO都对两种利什曼原虫具有强烈的细胞毒性,即使浓度很低也是如此。在相同的浓度下,BjussuLAAO-II和BmooLAAO-II对寄生虫产生不同的细胞毒性作用。我们首次报道了SV-LAAOs抑制了细胞增殖并改变了两个利什曼原虫的线粒体膜电位种类。出乎意料的是,BjussuLAAO-II仅在亚马逊L.(L.)中增加了细胞内活性氧的产生,而BmooLAAO-II仅在巴西L.(V.)中增加了细胞内活性氧的产生,表明这些SV-LAAO具有特定的动作。

更新日期:2020-12-04
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