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金属存在时自噬对克氏锥虫的消除作用。

Autophagic elimination of Trypanosoma cruzi in the presence of metals.

机构信息

Laboratory of Tissue and Cell Biology, State University of North Fluminense - Darcy Ribeiro, Campos dos Goytacazes, 28013-602, Rio de Janeiro, Brazil.

出版信息

J Microbiol. 2019 Oct;57(10):918-926. doi: 10.1007/s12275-019-9018-6. Epub 2019 Aug 28.

DOI:10.1007/s12275-019-9018-6
PMID:31463789
Abstract

Trypanosoma cruzi is an obligate intracellular parasite transmitted to vertebrate hosts by blood-sucking insects. Molecules present in parasites and mammalian cells allow the recognition and parasite internalization. Metallic ions play an essential role in the establishment and maintenance of host-parasite interaction. However, little is known about how parasites handle with essential and nonessential metal quotas. This study aimed to investigate the influence of metal ions on the biological processes of T. cruzi infected cells. Infected cells were incubated with ZnCl, CdCl, and HgCl for 12 h and labeled with different specific dyes to investigate the cellular events related to intracellular parasite death and elimination. Infected host cells and parasite's mitochondria underwent functional and structural disorders, in addition to parasite's DNA condensation and pH decrease on host cells, which led to parasite death. Further investigations suggested that lysosomes were involved in pH decrease and the double membrane of the endoplasmic reticulum formed vacuoles surrounding damaged parasites, which indicate the occurrence of autophagy for parasite elimination. In conclusion, low concentrations of nonessential and essential metals cause a series of damage to Trypanosoma cruzi organelles, leading to its loss of viability, death, and elimination, with no removal of the host cells.

摘要

克氏锥虫是一种专性细胞内寄生虫,通过吸血昆虫传播给脊椎动物宿主。寄生虫和哺乳动物细胞中存在的分子允许识别和寄生虫内化。金属离子在建立和维持宿主-寄生虫相互作用中起着至关重要的作用。然而,对于寄生虫如何处理必需和非必需金属配额知之甚少。本研究旨在研究金属离子对感染细胞的生物过程的影响。将感染细胞与 ZnCl、CdCl 和 HgCl 孵育 12 小时,并使用不同的特异性染料标记,以研究与细胞内寄生虫死亡和消除相关的细胞事件。感染的宿主细胞和寄生虫的线粒体经历了功能和结构障碍,此外,寄生虫的 DNA 凝聚和 pH 值降低也发生在宿主细胞上,这导致寄生虫死亡。进一步的研究表明,溶酶体参与 pH 值降低,内质网的双层形成围绕受损寄生虫的空泡,表明发生了自噬以消除寄生虫。总之,非必需和必需金属的低浓度会对克氏锥虫细胞器造成一系列损伤,导致其丧失活力、死亡和消除,而宿主细胞不受影响。

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本文引用的文献

1
Intracellular development of in the presence of metals.在金属存在的情况下的细胞内发育。 (你提供的原文“Intracellular development of in the presence of metals.”中“of”后面似乎缺少具体内容)
J Parasit Dis. 2018 Sep;42(3):372-381. doi: 10.1007/s12639-018-1010-2. Epub 2018 May 29.
2
Life and death of Trypanosoma cruzi in presence of metals.金属存在下克氏锥虫的生与死。
Biometals. 2017 Dec;30(6):955-974. doi: 10.1007/s10534-017-0064-4. Epub 2017 Oct 28.
3
Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes.重金属暴露影响双链断裂DNA修复结果。
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Highly stable and sensitive fluorescent probes (LysoProbes) for lysosomal labeling and tracking.用于溶酶体标记和追踪的高度稳定且灵敏的荧光探针(溶酶体探针)。
Sci Rep. 2015 Feb 26;5:8576. doi: 10.1038/srep08576.
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Mitochondrial metals as a potential therapeutic target in neurodegeneration.线粒体金属作为神经退行性疾病的潜在治疗靶点。
Br J Pharmacol. 2014 Apr;171(8):2159-73. doi: 10.1111/bph.12513.
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Trypanosoma cruzi: Entry into Mammalian Host Cells and Parasitophorous Vacuole Formation.克氏锥虫:进入哺乳动物宿主细胞和寄生空泡形成。
Front Immunol. 2013 Aug 1;4:186. doi: 10.3389/fimmu.2013.00186. eCollection 2013.
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Role of calcium channels in heavy metal toxicity.钙通道在重金属毒性中的作用。
ISRN Toxicol. 2013 Jan 30;2013:184360. doi: 10.1155/2013/184360. Print 2013.
9
Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury.金属、氧化应激与神经退行性变:关注铁、锰和汞。
Neurochem Int. 2013 Apr;62(5):575-94. doi: 10.1016/j.neuint.2012.12.006. Epub 2012 Dec 21.
10
The role of autophagy in host defence against Mycobacterium tuberculosis infection.自噬在宿主防御结核分枝杆菌感染中的作用。
Tuberculosis (Edinb). 2012 Sep;92(5):388-96. doi: 10.1016/j.tube.2012.05.004. Epub 2012 Jun 9.