Role of hsp105 in protection against stress-induced apoptosis in neuronal PC12 cells
Role of hsp105 in protection against stress-induced apoptosis in neuronal PC12 cells
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DOI：
10.1006/bbrc.2001.5802
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发表时间：
2001-11-02
影响因子：
3.1
通讯作者：
Sakai, K
中科院分区：
文献类型：
--
作者：
Hatayama, T;Yamagishi, N;Sakai, K
hsp105 α 是一种应激蛋白，与哺乳动物的其他组织相比，其特征是在大脑中高表达。在这里，为了检查 hsp105 α 是否在神经系统中发挥关键作用，我们测试了 hsp105a 防止大鼠神经元 PC12 细胞凋亡的能力。各种应激处理（例如血清剥夺、热休克、过氧化氢、依托泊苷和放线菌素 D）可诱导 PC12 细胞凋亡，并伴有细胞核和染色质的特征性收缩。然而，组成型过表达小鼠 hsp105a 的 PC12 细胞对这些应激处理诱导的细胞凋亡表现出强大的保护作用。在组成型过表达的 hsp105a 细胞中，这些处理在 PC12 细胞中诱导的聚（ADP-核糖）聚合酶的裂解受到抑制。此外，c-Jun N-末端激酶（JNK）在热休克处理的细胞中被激活，而其他处理则没有，并且热诱导的 JNK 激活被 hsp105 α 的组成型表达所抑制。因此，hsp105α不仅可以通过抑制JNK激活来防止热诱导的细胞凋亡，还可以通过不同途径防止其他应激源诱导的细胞凋亡，并可能在神经元保护中发挥重要作用。 (C) 2001 年学术出版社。
hsp105 alpha is a stress protein characteristically highly expressed in the brain compared with other tissues in mammals. Here, to examine whether hsp105 alpha plays a pivotal role in the nervous system, we tested the capability of hsp105a to protect against apoptosis in rat neuronal PC12 cells. Various stress treatments such as serum deprivation, heat shock, hydrogen peroxide, etoposide, and actinomycin D induced apoptosis in PC12 cells with characteristic shrinking of nuclei and chromatin. However, PC12 cells that constitutively overexpressed mouse hsp105a exhibited a strong protective effect against apoptosis induced by these stress treatments. Cleavage of poly(ADP-ribose) polymerase induced in PC12 cells by these treatments was inhibited in the constitutively overexpressed hsp105a cells. Furthermore, c-Jun N-terminal kinase (JNK) was activated in the cells treated with heat shock but not other treatments, and the heat-induced JNK activation was inhibited by the constitutive expression of hsp105 alpha. Thus, hsp105 alpha prevents not only heat-induced apoptosis by inhibiting JNK activation, but also prevents the apoptosis induced by other stressors through different pathways, and may play important roles in neuronal protection. (C) 2001 Academic Press.