The Potential Role of Sanguinarine as an Inhibitor of Leishmania PP2C in the Induction of Apoptosis

IF 1.2 3区 农林科学 Q4 PARASITOLOGY
M. Ornelas-Cruces, A. R. Escalona-Montaño, N. Salaiza-Suazo, S. Sifontes-Rodríguez, M. M. Aguirre-García
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引用次数: 0

Abstract

Leishmania spp. cause a wide range of human diseases, localized skin lesions, mucocutaneous and visceral infections. In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of Leishmania PP2C that can induce apoptosis in the parasite. The results demonstrated that sanguinarine inhibits, in a dose-dependent mode at 72 h, the growth and phosphatase activity of both Leishmania major and Leishmania mexicana promastigotes. Therefore, all assays were performed from this time period onwards. TUNEL assay was used to identify apoptosis and indicated apoptosis in L. major and L. mexicana promastigotes. Similarly, Western blot assay showed that PARP, a DNA damage indicator molecule, was present in L. major and L. mexicana promastigotes incubated with the inhibitor. In addition, differential expression of the proapoptotic protein Bax and the antiapoptotic protein Bcl-2 was observed in both Leishmania species. Finally, the protein phosphatase PP2C expression was not affected, whereas p38 MAPK phosphorylation was increased in L. major promastigotes than in L. mexicana promastigotes. Therefore, sanguinarine proved to be an inhibitor of the growth and PP2C enzymatic activity of L. major and L. mexicana promastigotes, and with it, this inhibition induced apoptosis.

血根碱作为利什曼原虫PP2C抑制剂在诱导凋亡中的潜在作用。
利什曼原虫引起广泛的人类疾病,局部皮肤病变,粘膜和内脏感染。在本研究中,目的是研究血根碱作为利什曼原虫PP2C特异性抑制剂的潜在作用,该抑制剂可以诱导利什曼原虫凋亡。结果表明,血根碱在72 h时以剂量依赖的方式抑制利什曼原虫和墨西哥利什曼原虫的生长和磷酸酶活性。因此,所有的化验都是从这一时期开始进行的。TUNEL法检测大L.和墨西哥L. promastigotes细胞凋亡及凋亡指示。同样,Western blot检测结果显示,与该抑制剂孵育的L. major和L. mexicana promastigotes中存在DNA损伤指示分子PARP。此外,在两种利什曼原虫中观察到促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的差异表达。最后,蛋白磷酸酶PP2C的表达不受影响,而p38 MAPK磷酸化在L. major promastigotes中比在L. mexicana promastigotes中增加。因此,血根碱可抑制L. major和L. mexicana promastigotes的生长和PP2C酶活性,并可诱导细胞凋亡。
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来源期刊
Acta Parasitologica
Acta Parasitologica 医学-寄生虫学
CiteScore
3.10
自引率
6.70%
发文量
149
审稿时长
6-12 weeks
期刊介绍: Acta Parasitologica is an international journal covering the latest advances in the subject. Acta Parasitologica publishes original papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in biochemical and molecular biology of parasites, their physiology, morphology, taxonomy and ecology, as well as original research papers on immunology, pathology, and epidemiology of parasitic diseases in the context of medical, veterinary and biological sciences. The journal also publishes short research notes, invited review articles, book reviews. The journal was founded in 1953 as "Acta Parasitologica Polonica" by the Polish Parasitological Society and since 1954 has been published by W. Stefanski Institute of Parasitology of the Polish Academy of Sciences in Warsaw. Since 1992 in has appeared as Acta Parasitologica in four issues per year.
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