HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis
HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis
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DOI：
10.1139/o11-083
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发表时间：
2012-04-01
影响因子：
2.9
通讯作者：
Scieglinska, Dorota
中科院分区：
文献类型：
--
作者：
Filipczak, Piotr Teodor;Piglowski, Wojciech;Scieglinska, Dorota
人类HSPA2是HSPA （HSP70）热休克蛋白家族的一员，由最初被描述为睾丸特异性的基因编码。最近，有报道称HSPA2也可以在人体体细胞组织中以细胞类型特异性的方式表达。本研究的目的是发现HSPA2是否可以增加体细胞对热休克、蛋白酶体抑制剂和几种抗癌细胞抑制剂的毒性作用的抵抗。我们使用了中国仓鼠成纤维细胞V79细胞系，因为这些细胞在正常培养条件下不表达HSPA2和细胞保护性HSPA1蛋白，并且在热休克和蛋白酶体抑制剂的反应中表达HSPA1的能力有限。我们通过逆转录病毒基因转移，建立了稳定的V79/HSPA2细胞系，该细胞系组成性地过表达HSPA2蛋白。我们研究的主要观察结果是HSPA2增加了经受热休克和蛋白酶体抑制剂的细胞的长期存活。我们发现，HSPA2对硼替佐米诱导的细胞凋亡具有抗性。因此，我们首次表明，在体细胞中，HSPA2可以成为保护细胞免受细胞毒性刺激诱导蛋白毒性应激的系统的一部分。
Human HSPA2 is a member of the HSPA (HSP70) family of heat-shock proteins, encoded by the gene originally described as testis-specific. Recently, it has been reported that HSPA2 can be also expressed in human somatic tissues in a cell-type specific manner. The aim of the present study was to find out whether HSPA2 can increase the resistance of somatic cells to the toxic effect of heat shock, proteasome inhibitors, and several anticancer cytostatics. We used a Chinese hamster fibroblast V79 cell line because these cells do not express the HSPA2 and cytoprotective HSPA1 proteins under normal culture conditions and show limited ability to express HSPA1 in response to heat shock and proteasome inhibitors. We established, by retroviral gene transfer, a stable V79/HSPA2 cell line, which constitutively overexpressed HSPA2 protein. The major observation of our study was that HSPA2 increased long-term survival of cells subjected to heat shock and proteasome inhibitors. We found, that HSPA2 confers resistance to bortezomib-induced apoptosis. Thus, we showed for the first time that in somatic cells HSPA2 can be a part of a system protecting cells against cytotoxic stimuli inducing proteotoxic stress.