DIFFERENTIAL REGULATION OF ACTIN POLYMERIZATION FOLLOWING ACTIVATION OF RESTING T-LYMPHOCYTES FROM YOUNG AND AGED MICE
DIFFERENTIAL REGULATION OF ACTIN POLYMERIZATION FOLLOWING ACTIVATION OF RESTING T-LYMPHOCYTES FROM YOUNG AND AGED MICE
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DOI：
10.1002/jcp.1041570221
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发表时间：
1993-11-01
影响因子：
5.6
通讯作者：
CHREST, F
中科院分区：
文献类型：
--
作者：
BROCK, MA;CHREST, F
肌动蛋白聚合伴随受体介导的反应，并与运动相关的事件。在T淋巴细胞中，存在表面受体侧向重新分布成帽和肌动蛋白-肌球蛋白聚集在胞质亚帽中，并且这些在来自老年个体的T细胞中受损。这项研究记录了与年龄相关的细胞骨架肌动蛋白丝功能的显着变化，这可能是运动性降低的原因。丝状肌动蛋白（F-肌动蛋白）的基础水平显着较高的纯化G，T细胞从老年C57 BL/6小鼠，由于优先增加的CD 8+亚群。在用伴刀豆球蛋白A（Con A）激活静息T细胞后，F-肌动蛋白在来自年轻小鼠的细胞中解聚2分钟，随后快速聚合，达到高于静息水平200%的平台。在来自15-17月龄小鼠的细胞中，观察到45秒的衰减解聚阶段，随后几乎没有聚合。老年小鼠细胞无解聚或聚合相发生。佛波醇12肉豆蔻酸酯13-乙酸酯（PMA）激活蛋白激酶C（PKC），绕过受体介导的信号，诱导年轻和老年动物细胞中肌动蛋白聚合水平达到ConA刺激后的57%，并部分消除了由于年龄引起的肌动蛋白丝组装的差异。细胞松弛素E（CE）的细胞骨架的扰动增强增殖的Con A刺激的T细胞从老年小鼠，但没有完全恢复的赤字归因于免疫衰老。结果表明，与年龄相关的细胞骨架功能的损害，并表明，早期信号转导事件的差异有助于减少表面受体的运动性和随后的增殖T淋巴细胞从老年人。(C)1993 Wiley-Liss，Inc.
Actin polymerization accompanies receptor-mediated responses and is correlated with motility-related events. In T lymphocytes, there is a lateral redistribution of surface receptors into caps and aggregation of actin-myosin in cytoplasmic sub-caps, and these are impaired in T cells from aged individuals. This study documents marked changes in age-related cytoskeletal actin filament function which may account for the reduced motility. Basal levels of filamentous actin (F-actin) are significantly higher in purified G, T cells from aged C57BL/6 mice, due to a preferential increase in the CD8+ subpopulation. Following activation of the resting T cells with Concanavalin A (Con A), F-actin depolymerized in cells from young mice for 2 min, followed by rapid polymerization, reaching a plateau 200% above resting levels. In cells from 15-17-month-old mice, an attenuated depolymerization phase was seen for 45 sec, followed by little polymerization. No depolymerization or polymerization phases occurred in cells from aged mice. Phorbol 12 myristate 13-acetate (PMA), which activates protein kinase C (PKC), bypassing receptor mediated signals, induced actin polymerization to 57% of the levels of that after Con A stimulation in cells from both young and old animals and partially eliminated the differences in actin filament assembly due to age. Perturbation of the cytoskeleton with cytochalasin E (CE) potentiated proliferation of Con A-stimulated T cells from aged mice but did not completely restore the deficit attributed to immunosenescence. The results show an age-related impairment of cytoskeletal functions and suggest that differences in early signal transduction events contribute to the decrements in surface receptor motility and subsequent proliferation of T lymphocytes from older individuals. (C) 1993 Wiley-Liss, Inc.