Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis.
Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis.
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DOI：
10.1001/archsurg.1997.01430360023004
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发表时间：
1997-12
影响因子：
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通讯作者：
S. A. Gordon;R. Hoffman;R. Simmons;H. Ford
中科院分区：
文献类型：
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作者：
S. A. Gordon;R. Hoffman;R. Simmons;H. Ford
目的：研究热休克蛋白70 （hsp70）的诱导是否会保护胸腺细胞和t细胞克隆免受辐射诱导的凋亡，并确定这种保护的机制。热休克蛋白70是一种具有细胞保护作用并在各种刺激下抑制细胞死亡的应激蛋白。BALB/c小鼠胸腺细胞或t淋巴细胞克隆在43℃下孵育1小时，诱导hsp70，然后辐照。对照细胞辐照但不加热。定量DNA片段化，用Western blot法分析不同时间p53、bax、bcl-2的表达。结果只有加热后的细胞表达hsp70。hsp70的诱导增加了基底细胞凋亡，但显著减少了辐射诱导的细胞凋亡。此外，在加热之前引入HSP 70反义寡聚物逆转了HSP 70的保护作用。亚砷酸钠诱导t细胞克隆的hsp70对辐射诱导的细胞凋亡具有类似的保护作用。辐照诱导p53和bax显著上调。p53的表达在4小时达到峰值，并先于最大bax诱导。在辐照前诱导hsp70抑制p53并显著降低bax水平。bcl-2水平未受影响。结论：hsp70诱导通过下调p53和bax的表达来保护胸腺细胞免受辐射诱导的凋亡。hsp70的诱导可能代表了一种新的机制，通过这种机制可以将放射治疗的免疫抑制效应和相关的感染并发症降到最低。
OBJECTIVES To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. DESIGN Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43 degrees C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, bax, and bcl-2 expression was analyzed at various times by the Western blot method. RESULTS Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T-cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly up-regulated bax. The expression of p53 peaked at 4 hours and preceded maximal bax induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased bax levels. Levels of bcl-2 were unaffected. CONCLUSIONS Our data show that HSP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and bax expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.