Caspase-3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation
Caspase-3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation
复制标题
DOI：
10.1002/glia.20518
复制
发表时间：
2007-07-01
期刊：
影响因子：
6.2
通讯作者：
Gonzalez, Berta
中科院分区：
文献类型：
--
作者：
Acarin, Laia;Villapol, Sonia;Gonzalez, Berta
Caspase-3 传统上被定义为程序性细胞死亡的主要执行者。然而，最近的数据支持这种蛋白酶参与非凋亡细胞事件，包括细胞增殖、细胞周期调节和细胞分化。在这项研究中，分析了出生后大鼠兴奋性毒性损伤后星形胶质细胞 caspase-3 的裂解，以确定其存在是否与细胞凋亡、细胞增殖或细胞骨架重塑相关。研究了一种充分表征的兴奋性毒性体内模型，通过在出生后第 9 天的大鼠皮质内注射 N-甲基-D-天冬氨酸 (NMDA) 来诱导损伤。我们的结果表明，裂解的 caspase-3 早在损伤后 4 小时就主要在损伤半球激活的星形胶质细胞的细胞核中观察到，并持续到 7-14 天神经胶质疤痕形成，并且与 TUNEL 标记无关。在星形胶质细胞损伤后 10 小时和 1 天检测到 Caspase-3 酶活性，并与胶质纤维酸性蛋白 (CCPGFAP) 的 caspase 切割片段共定位。然而，在较长的生存时间内，当观察到星形胶质细胞肥大时，星形胶质细胞 caspase-3 通常与 GFAP 裂解无关，而是与波形蛋白的从头表达相关。此外，星形胶质细胞 caspase-3 裂解与 BrdU 掺入无关。这些结果为半胱天冬酶在细胞功能中独立于细胞死亡的非传统作用提供了进一步的证据，并表明半胱天冬酶激活对于细胞损伤后星形胶质细胞骨架重塑很重要。 (C) 2007 Wiley-Liss, Inc.
Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well-characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N-methyl-D-asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase-3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7-14 days, and it was not associated with TUNEL labeling. Caspase-3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co-localized with caspase-cleaved fragments of glial fibrillary acidic protein (CCPGFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase-3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase-3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury. (C) 2007 Wiley-Liss, Inc.