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寄生虫自噬和凋亡表型的时间分析

Temporal analysis of the autophagic and apoptotic phenotypes in parasites.

作者信息

Basmaciyan Louise, Berry Laurence, Gros Julie, Azas Nadine, Casanova Magali

机构信息

UMR PAM A, Valmis team, 2 rue Angélique Ducoudray, BP 37013, 21070 Dijon Cedex, France.

Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR 5235, University of Montpellier, France.

出版信息

Microb Cell. 2018 Aug 1;5(9):404-417. doi: 10.15698/mic2018.09.646.

Abstract

The leishmaniases are worldwide neglected tropical diseases caused by parasitic protozoa of the genus. Different stimuli induce cell death, but the proteins involved remain poorly understood. Furthermore, confusion often appears between cell death and the cell survival process autophagy, whose phenotype is not clearly defined. In this article, we present a comprehensive and temporal analysis of the cellular events occurring during miltefosine-induced cell death and autophagy in . We also provide a list of features in order to clearly identify apoptotic cells, autophagic cells and to distinguish both processes. Furthermore, we demonstrate that autophagy is followed by apoptosis in the absence of nutrients. Finally, we show that cells treated with the generic kinase inhibitor staurosporine express apoptotic as well as autophagic markers and therefore cannot be used as an apoptosis inducer in . These descriptions lead to a better recognition and understanding of apoptosis and autophagy, enabling their targeting in the development of new anti-leishmanial drugs. These researches also make it possible to better understand these processes in general, through the study of an ancestral eukaryote.

摘要

利什曼病是由该属寄生原生动物引起的全球被忽视的热带病。不同的刺激会诱导细胞死亡,但其中涉及的蛋白质仍知之甚少。此外,细胞死亡与细胞存活过程自噬之间常常出现混淆,自噬的表型尚未明确界定。在本文中,我们对米替福新诱导细胞死亡和自噬过程中发生的细胞事件进行了全面的时间分析。我们还提供了一系列特征,以便清晰地识别凋亡细胞、自噬细胞并区分这两个过程。此外,我们证明在缺乏营养的情况下,自噬之后会发生凋亡。最后,我们表明用通用激酶抑制剂星形孢菌素处理的细胞同时表达凋亡和自噬标志物,因此不能用作诱导细胞凋亡的试剂。这些描述有助于更好地识别和理解凋亡与自噬,从而在开发新的抗利什曼原虫药物时对其进行靶向作用。通过对一种原始真核生物的研究,这些研究还使得总体上更好地理解这些过程成为可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c2/6167523/88035dac24dd/mic-05-404-g01.jpg

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