General Commentary a Fine Balance between Life and Death: Modulation of Bcl-2 Family Members by Toxoplasma Gondii a Commentary on the Differential Effect of Toxoplasma Gondii Infection on the Stability of Bcl2-family Members Involves Multiple Activities
General Commentary a Fine Balance between Life and Death: Modulation of Bcl-2 Family Members by Toxoplasma Gondii a Commentary on the Differential Effect of Toxoplasma Gondii Infection on the Stability of Bcl2-family Members Involves Multiple Activities
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Gustavo Arrizabalaga;Carmen;Sinai
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作者：
Gustavo Arrizabalaga;Carmen;Sinai
细胞凋亡已被证明是一种机制，通过这种机制，感染了病毒、细菌或细胞内寄生虫的细胞可以被清除，而不会引发不必要的炎症反应。毫不奇怪，细胞内病原体已经进化出抑制细胞凋亡的机制，不仅避免了宿主细胞的消除，而且还延长了它的寿命。细胞内病原体对细胞凋亡的抑制是通过影响感染细胞中促凋亡和抗凋亡因子之间的微妙平衡来实现的。各种微生物利用的一种机制是调节bcl2家族的促凋亡和抗凋亡蛋白(Carmen和Sinai，2007；Faherty和Maurelli，2008；Galluzzi等人，2008)。BCL-2家族包括促凋亡蛋白BCL-2相关的X蛋白(BAX)和BCL-2拮抗剂/杀手-1(BAK)，它们直接参与线粒体细胞色素C的释放(Youle和Strasser，2008)。BCL-2家族的其他成员(如BAD、BID、BIM)参与Bax或BAK的直接或间接激活，从而具有促凋亡作用，而其他成员(如BCL-2和BCL-XL)则抑制这些孔形成蛋白，从而起到抗凋亡作用(Youle和Strasser，2008)。在最近的一篇前沿细胞和感染微生物学研究文章中，Carmen和Sinai(2011)表明弓形虫是人类和其他动物的一种重要致病原性寄生虫，通过不同的蛋白分解活性影响几个bcl2家族蛋白的稳定性。为了确保其在受感染宿主内的存活和成功繁殖，弓形虫抑制受感染细胞的凋亡。与弓形虫感染相关的抗凋亡事件包括激活核因子-κB(核因子-κB)，抑制磷脂酰肌醇3-激酶(PI3-K)，从有丝分裂释放细胞色素C，以及直接抑制端粒体活性(Carmen和Sinai，2007年综述；Laliberte和Carruthers，2008)。据报道，阻止弓形虫感染细胞中细胞色素C的释放与bcl2转录水平的增加、线粒体靶向的抑制和bax的激活(Hippe等人，2009年)以及促凋亡蛋白Bax、Bad和Bid的选择性降解有关(Goebel等人，2001年；Molestina等人，2003年)。在沙眼衣原体等其他病原体中也观察到bcl2家族促凋亡成员的降解(董等人，2005年)。为了更好地确定依赖弓形虫的bcl2家族蛋白降解的要求，Carmen和Sinai(2011年)分析了不同感染复数(MOI)和…中bcl2家族蛋白的水平
Apoptosis has been shown to serve as a mechanism by which cells infected with viruses, bacteria, or intracellular parasites can be eliminated without eliciting an unwanted inflammatory response. Not surprisingly intracellular pathogens have evolved mechanisms by which to inhibit apoptosis, not only avoiding the elimination of the host cell but also extending its life span. Inhibition of apoptosis by intracellu-lar pathogens is accomplished by affecting the fine balance between pro-and anti-apoptotic factors in the infected cell. One mechanism utilized by various microbes is regulation of the pro-and anti-apoptotic proteins of the BCL-2 family (Carmen and Sinai, 2007; Faherty and Maurelli, 2008; Galluzzi et al., 2008). The BCL-2 family includes the pro-apoptotic proteins BCL-2-associated X protein (BAX) and the BCL-2 antagonist/killer-1 (BAK), which directly participate in the release of Cytochrome C from mitochondria (Youle and Strasser, 2008). Other members of the BCL-2 family (e.g., BAD, BID, BIM) participate in the direct or indirect activation of BAX or BAK, thus having pro-apoptotic effects, while others (e.g., BCL-2 and BCL-XL) inhibit these pore forming proteins, thus acting as anti-apoptotic agents (Youle and Strasser, 2008). In a recent Frontiers in Cellular and Infection Microbiology research article , Carmen and Sinai (2011) show that Toxoplasma gondii, an important patho-genic parasite of humans and other animals , affects the stability of several BCL-2 family proteins via a diversity of proteolytic activities. In order to ensure its survival and successful propagation within an infected host, T. gondii inhibits apoptosis in infected cells. Anti-apoptotic events associated with T. gondii infection include activation of the nuclear factor-κ B (NF-κB) inhibition of phosphoinositide 3-kinase (PI3-K), Cytochrome C release from the mitochon-drion, and direct inhibition of the apop-tosome activity (reviewed in Carmen and Sinai, 2007; Laliberte and Carruthers, 2008). Obstruction of Cytochrome C release in T. gondii infected cells has been reported to correlate with increase of BCL-2 transcript level inhibition of mitochondrial targeting and activation of BAX (Hippe et al., 2009), as well as selective degradation of the pro-apoptotic proteins BAX, BAD, and BID (Goebel et al., 2001; Molestina et al., 2003). Degradation of pro-apoptotic members of the BCL-2 family is also observed with other pathogens such as Chlamydia trachomatis (Dong et al., 2005). To better define the requirements for the T. gondii dependent degradation of BCL-2 family proteins, Carmen and Sinai (2011) have now analyzed the levels of BCL-2 family proteins at varying multiplicities of infection (MOI) and in …