Proteasome inhibition increases HuR level, restores heat-inducible HSP72 expression and thermotolerance in WI-38 senescent human fibroblasts
Proteasome inhibition increases HuR level, restores heat-inducible HSP72 expression and thermotolerance in WI-38 senescent human fibroblasts
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DOI：
10.1016/j.exger.2003.12.004
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发表时间：
2004-03-01
影响因子：
3.9
通讯作者：
Borghetti, AF
中科院分区：
文献类型：
--
作者：
Bonelli, MA;Alfieri, RR;Borghetti, AF
在其体外复制潜力的末期，晚期传代WI-38人二倍体成纤维细胞（HDF）具有热休克蛋白72（HSP 72）的低基础表达和响应于热休克诱导HSP 72的减弱能力。在轻度热休克期间短暂暴露于特异性和可逆性蛋白酶体抑制剂MG 132诱导晚期传代HDF合成和蓄积高水平的HSP 72。这种HSP 72表达是持久的，似乎是由于细胞质水平的增加和HSP 72 mRNA翻译的增强。在MG 132处理后，HuR（一种稳定mRNA结合蛋白）的水平增加。这一结果与HuR在协助mRNA输出到细胞质和拮抗其降解中的作用一致。此外，先前在存在MG 132的情况下将晚期传代HDF暴露于轻度热休克可保护这些细胞免受随后重度热休克的其他致死作用。热耐受性的获得似乎与HSP 72的水平相关。(C)2004年爱思唯尔公司All rights reserved.
At the end of their replicative potential in vitro, late passage WI-38 human diploid fibroblasts (HDF) have a low basal expression of heat shock protein 72 (HSP72) and an attenuated ability to induce it in response to heat shock. The transient exposure to the specific and reversible proteasome inhibitor MG132 during a mild heat shock induced late passage HDF to synthesize and accumulate high levels of HSP72. This HSP72 expression was long-lasting and appeared to result from both increased cytoplasmic levels and enhanced translation of HSP72 mRNA. The level of HuR, a stabilizing mRNA-binding protein, increased following the MG132 treatment. This result is consistent with the proposed role of HuR in assisting mRNA export to the cytoplasm and in antagonizing its degradation. Furthermore, the previous exposure of late passage HDF to a mild heat shock in the presence of MG132 protected these cells against the otherwise lethal effect of a subsequent severe heat shock. This acquisition of thermotolerance appeared to be correlated with the level of HSP72. (C) 2004 Elsevier Inc. All rights reserved.