REGULATION OF HEAT-SHOCK PROTEIN-SYNTHESIS BY QUERCETIN IN HUMAN ERYTHROLEUKEMIA-CELLS
REGULATION OF HEAT-SHOCK PROTEIN-SYNTHESIS BY QUERCETIN IN HUMAN ERYTHROLEUKEMIA-CELLS
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DOI：
10.1042/bj3000201
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发表时间：
1994-05-15
影响因子：
4.1
通讯作者：
SANTORO, MG
中科院分区：
文献类型：
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作者：
ELIA, G;SANTORO, MG
热休克蛋白（HSPs）的合成普遍诱导真核和原核细胞暴露于高温或其他类型的环境应力。在哺乳动物细胞中，属于70 kDa家族（HSP 70）的HSP在几种细胞过程中具有调节作用，并且已经显示参与控制细胞增殖和分化。虽然已经鉴定了许多类型的HSP 70诱导剂，但是只有少数化合物（全部属于类黄酮组）已经显示出抑制HSP 70诱导。由于HSP 70合成的抑制剂可能是一个重要的工具，研究这种蛋白质的功能，我们已经研究了槲皮素，一种黄酮类化合物，具有抗增殖活性，广泛分布在自然界中，对HSP 70的合成在人K562红白血病细胞治疗后，严重或轻度的热休克和其他诱导剂。槲皮素被发现影响HSP 70的合成在一个以上的水平，这取决于所使用的条件。事实上，在严重的热休克（45 ℃，20分钟）后，发现用无毒浓度的槲皮素处理抑制HSP 70合成3-4小时。这种阻断似乎是在转录后水平发挥作用的，并且是细胞介导的，因为在体外HSP 70 mRNA翻译过程中添加槲皮素没有影响。然而，在43 ℃下长时间（90分钟）暴露后，发现槲皮素也抑制HSP 70 mRNA转录。用槲皮素预处理K562细胞对HSP 70表达没有影响，槲皮素需要在诱导过程中存在才有效。在所有测试条件下，发现槲皮素诱导的HSP 70合成阻滞是短暂的，并且在初始延迟之后，HSP 70的合成达到控制速率，并且在HSP 70合成在控制细胞中被关闭的时间之后在相同水平持续几个小时。最后，抑制热休克蛋白70的合成槲皮素似乎是依赖于所使用的温度和压力的类型。
Synthesis of heat-shock proteins (HSPs) is universally induced in eukaryotic and prokaryotic cells by exposure to elevated temperatures or to other types of environmental stress. In mammalian cells, HSPs belonging to the 70 kDa family (HSP70) have a regulatory role in several cellular processes, and have been shown to be involved in the control of cell proliferation and differentiation. Although many types of HSP70 inducers have been identified, only a few compounds, all belonging to the flavonoid group, have been shown to inhibit HSP70 induction. Because inhibitors of HSP70 synthesis could be an important tool with which to study the function of this protein, we have investigated the effect of quercetin, a flavonoid with antiproliferative activity which is widely distributed in nature, on HSP70 synthesis in human K562 erythroleukaemia cells after treatment with severe or mild heat shock and with other inducers. Quercetin was found to affect HSP70 synthesis at more than one level, depending on the conditions used. Indeed, after severe heat shock (45 degrees C for 20 min) treatment with quercetin, at non-toxic concentrations, was found to inhibit HSP70 synthesis for a period of 3-4 h. This block appeared to be exerted at the post-transcriptional level and to be cell-mediated, as the addition of quercetin during translation of HSP70 mRNA in vitro had no effect. After prolonged (90 min) exposure at 43 degrees C, however, quercetin was found to inhibit also HSP70 mRNA transcription. Pretreatment of K562 cells with quercetin had no effect on HSP70 expression, and quercetin needed to be present during induction to be effective. Under all conditions tested, the quercetin-induced block of HSP70 synthesis was found to be transient and, after an initial delay, synthesis of HSP70 reached the control rate and continued at the same level for several hours after the time at which HSP70 synthesis had been turned off in control cells. Finally, inhibition of HSP70 synthesis by quercetin appeared to be dependent on the temperature used and on the type of stressor.