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寄生虫死亡时诱导的泰勒虫感染淋巴细胞凋亡涉及半胱天冬酶9和3的激活。

Apoptosis of Theileria-infected lymphocytes induced upon parasite death involves activation of caspases 9 and 3.

作者信息

Guergnon Julien, Dessauge Frédéric, Langsley Gordon, Garcia Alphonse

机构信息

Département de Parasitologie, URA CNRS 2581, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France.

出版信息

Biochimie. 2003 Aug;85(8):771-6. doi: 10.1016/j.biochi.2003.09.013.

Abstract

The intracellular parasite Theileria parva (T. parva) can infect bovine B and T-lymphocytes. T. parva-infected cells become transformed, and they survive and proliferate independently of exogenous growth factors. In vivo the uncontrolled cellular proliferation associated with lymphocyte transformation underlies the pathogenesis of the disease called East Coast Fever. The transformed state of parasitised cells can be reversed upon elimination of the parasite by specific theilericide drugs. In this study we found that elimination of the parasite by buparvaquone induces apoptosis of transformed B and CD8(+) T-lymphocytes. Apoptosis is accompanied by the activation of caspase 9 and caspase 3 and processing of poly(ADP ribose) polymerase and is inhibited by Z-VAD a general caspase inhibitor. Based on these observations, we propose that the lack of activation of a caspase 9 > caspase 3 > poly(ADP ribose) polymerase pathway is important and protects T. parva-transformed cells from spontaneous apoptosis.

摘要

细胞内寄生虫微小泰勒虫(T. parva)可感染牛的B淋巴细胞和T淋巴细胞。被T. parva感染的细胞会发生转化,并且它们能够独立于外源性生长因子存活和增殖。在体内,与淋巴细胞转化相关的不受控制的细胞增殖是称为东海岸热的疾病发病机制的基础。通过特定的杀泰勒虫药物消除寄生虫后,被寄生细胞的转化状态可以逆转。在本研究中,我们发现通过丁萘脒消除寄生虫会诱导转化的B淋巴细胞和CD8(+) T淋巴细胞凋亡。凋亡伴随着半胱天冬酶9和半胱天冬酶3的激活以及聚(ADP核糖)聚合酶的加工,并且被通用的半胱天冬酶抑制剂Z-VAD抑制。基于这些观察结果,我们提出半胱天冬酶9>半胱天冬酶3>聚(ADP核糖)聚合酶途径缺乏激活是重要的,并且可保护T. parva转化的细胞免于自发凋亡。

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