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硕大利什曼原虫端粒酶TERT蛋白具有受氧化应激影响的核/线粒体重叠分布。

Leishmania major telomerase TERT protein has a nuclear/mitochondrial eclipsed distribution that is affected by oxidative stress.

作者信息

Campelo Riward, Díaz Lozano Isabel, Figarella Katherine, Osuna Antonio, Ramírez José Luis

机构信息

Instituto de Estudios Avanzados, Centro de Biotecnologia, MppEUCT, Caracas, Venezuela.

Molecular Parasitology Research Group, Institute of Biotechnology, Department of Parasitology, Faculty of Science, University of Granada, Granada, Spain.

出版信息

Infect Immun. 2015 Jan;83(1):57-66. doi: 10.1128/IAI.02269-14. Epub 2014 Oct 13.

Abstract

In its canonical role the reverse transcriptase telomerase recovers the telomeric repeats that are lost during DNA replication. Other locations and activities have been recently described for the telomerase protein subunit TERT in mammalian cells. In the present work, using biochemistry, molecular biology, and electron microscopy techniques, we found that in the human parasite Leishmania major, TERT (and telomerase activity) shared locations between the nuclear, mitochondrial, and cytoplasmic compartments. Also, some telomerase activity and TERT protein could be found in ∼ 100-nm nanovesicles. In the mitochondrial compartment, TERT appears to be mainly associated with the kinetoplast DNA. When Leishmania cells were exposed to H2O2, TERT changed its relative abundance and activity between the nuclear and mitochondrial compartments, with the majority of activity residing in the mitochondrion. Finally, overexpression of TERT in Leishmania transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress.

摘要

在其典型作用中,逆转录酶端粒酶可恢复在DNA复制过程中丢失的端粒重复序列。最近在哺乳动物细胞中发现了端粒酶蛋白亚基TERT的其他定位和活性。在本研究中,我们使用生物化学、分子生物学和电子显微镜技术发现,在人类寄生虫硕大利什曼原虫中,TERT(和端粒酶活性)在细胞核、线粒体和细胞质区室之间共享定位。此外,在约100纳米的纳米囊泡中可发现一些端粒酶活性和TERT蛋白。在线粒体区室中,TERT似乎主要与动质体DNA相关。当利什曼原虫细胞暴露于过氧化氢时,TERT改变了其在细胞核和线粒体区室之间的相对丰度和活性,大部分活性存在于线粒体中。最后,在转染的利什曼原虫细胞中过表达TERT不仅提高了寄生虫细胞的生长速率,还增强了它们对氧化应激的抗性。

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