Ornelas-Cruces M, Escalona-Montaño A R, Salaiza-Suazo N, Sifontes-Rodríguez S, Aguirre-García M M
Laboratorio de Estudios Sociales de la Ciencia y la Tecnología, Departamento de Biología Evolutiva, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, México.
División de Investigación, Facultad de Medicina, Unidad de Investigación UNAM-INC, Universidad Nacional Autónoma de México, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Ciudad de México, C.P. 14080, México.
Acta Parasitol. 2025 Jan 24;70(1):35. doi: 10.1007/s11686-024-00977-x.
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.
利什曼原虫属会引发多种人类疾病，包括局部皮肤病变、黏膜皮肤感染和内脏感染。在本研究中，目的是探究血根碱作为利什曼原虫PP2C的特异性抑制剂的潜在作用，该抑制剂可诱导寄生虫凋亡。结果表明，血根碱在72小时时以剂量依赖方式抑制硕大利什曼原虫和墨西哥利什曼原虫前鞭毛体的生长及磷酸酶活性。因此，所有实验均从该时间段开始进行。TUNEL检测用于鉴定凋亡，结果表明硕大利什曼原虫和墨西哥利什曼原虫前鞭毛体均发生了凋亡。同样，蛋白质印迹检测显示，与抑制剂孵育的硕大利什曼原虫和墨西哥利什曼原虫前鞭毛体中存在DNA损伤指示分子PARP。此外，在这两种利什曼原虫中均观察到促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的差异表达。最后，蛋白质磷酸酶PP2C的表达未受影响，而硕大利什曼原虫前鞭毛体中的p38丝裂原活化蛋白激酶磷酸化程度高于墨西哥利什曼原虫前鞭毛体。因此，血根碱被证明是硕大利什曼原虫和墨西哥利什曼原虫前鞭毛体生长及PP2C酶活性的抑制剂，并且这种抑制作用可诱导凋亡。
