Intracellular accumulation of cell cycle regulatory proteins and nucleolin re-localization are associated with pre-lethal ultrastructural lesions in circulating T lymphocytes: The HIV-induced cell cycle dysregulation revisited
Intracellular accumulation of cell cycle regulatory proteins and nucleolin re-localization are associated with pre-lethal ultrastructural lesions in circulating T lymphocytes: The HIV-induced cell cycle dysregulation revisited
复制标题
DOI：
10.4161/cc.9.11.11754
复制
发表时间：
2010-06
期刊：
影响因子：
4.3
通讯作者：
G. Visalli;M. Paiardini;C. Chirico;B. Cervasi;M. Currò;N. Ferlazzo;M. Bertuccio;A. Favaloro;G. Pellicanò;P. Spataro;R. Ientile;I. Picerno;G. Piedimonte
中科院分区：
文献类型：
--
作者：
G. Visalli;M. Paiardini;C. Chirico;B. Cervasi;M. Currò;N. Ferlazzo;M. Bertuccio;A. Favaloro;G. Pellicanò;P. Spataro;R. Ientile;I. Picerno;G. Piedimonte
HIV诱导的CD 4-T细胞死亡被认为是淋巴组织中发生的遗传程序性细胞死亡的结果，其中许多常驻T细胞长期过度活化。由于HIV诱导的细胞周期调控的改变通常被认为是免疫超活化的重要机制和凋亡性死亡的原因，因此HIV感染患者T淋巴细胞周期失调的信号通路被广泛研究。在这里，我们还表明，循环T淋巴细胞离开淋巴组织扩散退化病变（空泡化，起泡，核消失和细胞器肿胀）。同样扩散的是伴随细胞结构整体紊乱的生化异常，特别是C23/核仁蛋白的碎片化和扩散到细胞质中，短寿命调节蛋白的细胞内积累和膜蛋白表达的减少。所有这些都不仅仅是细胞形态和生化机制的细胞周期相关重塑，而是回忆起坏死/肿瘤细胞损伤。由于这些变化与缺氧的适应机制有关，因此我们提供了在缺乏能量供应的条件下改变细胞周期控制的证据。
The HIV-induced demise of CD4-T cells is thought to be a result of the execution of genetically programmed cell death that occurs in lymphoid tissue, where many resident T cells are chronically hyperactivated. Since HIV-induced alterations of cell cycle control has been often indicated as prominent mechanism of immune hyper activation and cause of apoptotic death, the signal pathway involved in cell cycle dysregulation of T lymphocytes from HIV infected patients was extensively studied. Here, we also demonstrate that circulating T lymphocytes leave lymphoid tissues with diffused regressive lesions (vacuolization, blebbing, nuclear evanescence and organelle swelling). Equally diffused are biochemical anomalies that accompany the overall disarrangement of cell structure, particularly the fragmentation and diffusion into the cytoplasm of C23/nucleolin, the intracellular accumulation of short lived regulatory proteins and the decrease in expression of membrane proteins. All this is something more than a cell cycle-related remodelling of cell morphology and biochemical mechanisms, and rather recalls a necrotic/oncotic cell damage. Since these changes are associated with adaptive mechanisms to hypoxia, we give evidence for alteration of cell cycle control developing in conditions of scarce energy supply.