Increased heat shock protein 90 (hsp90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-alpha and cycloheximide: a possible role in immunopathology.
Increased heat shock protein 90 (hsp90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-alpha and cycloheximide: a possible role in immunopathology.
复制标题
在用 TNF-α 和放线菌酮诱导后，热休克蛋白 90 (hsp90) 表达增加导致单胚细胞系 U937 细胞凋亡增加：可能在免疫病理学中发挥作用。
作者：
Joanna Galea;A. Richardson;D. S. Latchman;David R. Katz
在这项研究中，我们检验了热休克蛋白（hsp）（如hsp 72和hsp 90）参与调节导致程序性细胞死亡的细胞损伤形式的假设。单胚细胞系U937已被用作模型系统。对于热休克蛋白90，这是不是热诱导在这个细胞系中，我们使用稳定的U937转染，无论是高表达或低表达的蛋白质。对于热休克蛋白72（这是可重复地诱导在所有三个细胞系相对较高的表达水平），我们研究了U937细胞热休克前后。我们发现，细胞凋亡确实发生在单核细胞/单核吞噬细胞谱系，它可以在体外诱导血清剥夺，紫外线，或TNF-α与放线菌酮（CX）的组合。然而，当细胞用TNF-α和cx的组合处理时，过量的hsp 90与增加的凋亡相关，而当它们暴露于UV B辐射时则不相关。这是补充的发现，降低hsp 90水平与保护对TNF-α和CX处理的细胞凋亡。此外，新合成的热休克蛋白72不能防止细胞凋亡。因此，热休克蛋白90水平可能发挥作用，在控制单核吞噬细胞在免疫病理学中发挥的作用。
In this study, we examined the hypothesis that heat shock proteins (hsp) (such as hsp72 and hsp90) are implicated in the regulation of forms of cell injury that lead to programmed cell death. The monoblastoid cell line U937 has been used as a model system. For hsp90, which is not heat inducible in this cell line, we used stable U937 transfectants that either hyperexpress or hypoexpress the protein. For hsp72 (which is reproducibly induced in all three cell lines to relatively high levels of expression), we studied U937 cells before and after heat shock. We showed that apoptosis does occur in the monoblast/mononuclear phagocyte lineage, and that it could be induced in vitro by serum deprivation, UV light, or TNF-alpha in combination with cycloheximide (cx). However, an excess of hsp90 is associated with increased apoptosis when the cells are treated with a combination of TNF-alpha and cx but not when they are exposed to UV B radiation. This was complemented by the finding that reduced hsp90 levels correlate with protection against apoptosis in the TNF-alpha- and cx-treated cells. Furthermore, new synthesis of hsp72 does not protect against apoptosis. Thus, hsp90 levels may play a role in controlling the part played by mononuclear phagocytes in immunopathology.