Bleomycin induces the hsp 70 heat shock promoter in cultured cells.
Bleomycin induces the hsp 70 heat shock promoter in cultured cells.
复制标题
博莱霉素在培养细胞中诱导 hsp 70 热休克启动子。
DOI：
10.1165/ajrcmb/1.2.89
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发表时间：
1989
影响因子：
6.4
通讯作者：
York,J
中科院分区：
文献类型：
--
作者：
Moseley,PL;York,SJ;York,J
博莱霉素诱导的肺部疾病的特征是细胞损伤，然后是成纤维细胞增殖。细胞通过合成热休克蛋白家族对损伤作出反应。这些蛋白质对细胞存活至关重要，而70000 MW组（hsp 70）的蛋白质对细胞分裂和增殖至关重要。为了评估博来霉素对热休克基因表达的影响，我们将含有热休克基因启动子hsp70的基因构建体转染成纤维细胞。博莱霉素的剂量，先前已被证明可以增强肺成纤维细胞的增殖，在转染的细胞中诱导hsp70热休克启动子。博莱霉素没有诱导非热休克蛋白启动子的表达，将其置于细胞中作为非特异性基因激活的控制。这些观察结果表明，博来霉素暴露可能导致重要DNA启动子区域（如hsp70启动子）的显著改变，并指出了评估博来霉素诱导的细胞变化的新方法。博来霉素是一种化疗药物，可用于治疗睾丸癌、淋巴瘤和鳞状细胞癌。临床上，多达25%的接受博来霉素治疗的患者发生肺毒性，博来霉素引起的肺损伤已成为间质性肺炎和肺纤维化的实验模型（1-4）。
Bleomycin-induced lung disease is characterized by cell injury followed by fibroblast proliferation. Cells respond to injury by synthesizing a family of heat shock proteins. These proteins are critical to cell survival, and those of the 70,000 MW group (hsp 70) are essential for cell division and proliferation. To evaluate the effect of bleomycin on heat shock gene expression, we transfected a gene construct containing the hsp 70 heat shock gene promoter into fibroblasts. Doses of bleomycin, which have previously been shown to augment lung fibroblast proliferation, induce the hsp 70 heat shock promoter in the transfected cells. Bleomycin did not induce the expression of a non-hsp promoter placed in cells as a control of nonspecific gene activation. These observations suggest that bleomycin exposure may cause significant alterations in important DNA promoter regions such as the hsp 70 promoter and point to new ways to assess bleomycin-induced changes in cells.Bleomycin is a chemotherapeutic agent that is useful in the treatment oftesticular carcinoma, lymphoma, and squamous cell carcinoma. Clinically, pulmonary toxicity occurs in as many as 25% of patients receiving bleomycin, and bleomycin-induced pulmonary damage has become an experimental model for interstitial pneumonitis and pulmonary fibrosis (1-4).