Cechowska-Pasko Marzanna, Bankowski Edward, Chene Patrick
Novartis Oncology Department, Basel, Switzerland.
Cell Physiol Biochem. 2006;17(1-2):89-96. doi: 10.1159/000091467. Epub 2006 Feb 7.
Correct protein folding is an important factor, for the translocation of newly synthesised proteins to specific subcellular compartments, extracellular matrix or to biological fluids. This process is regulated by a group of specific proteins, referred to as chaperones. Many stress conditions, such as oxygen or glucose deprivation, slow down the folding process and cause accumulation of unfolded/misfolded proteins in the cell. Molecular chaperones are induced in these conditions; with some named as oxygen-regulated proteins (ORPs). These bind to unfolded / misfolded proteins to facilitate correct assembly. ORP 150 is the subject of this study. Hypoxia results in an enhancement of ORP 150 expression in several tumour cell lines cultured in vitro. HeLa cells grown in hypoxic conditions (despite an intensive expression of ORP 150) demonstrate higher rates of apoptosis in comparison to those cultured in normoxic conditions. Furthermore, the inhibition of ORP 150 synthesis by transfection of these cells with a specific siRNA resulted in an intensification of apoptosis, as indicated by specific markers of this process; the enhancement of poly ADP-ribose protein cleavage and the increase in Bim protein expression. We conclude from our study that the increase in ORP 150 synthesis protects the cells against the proapoptotic effect of hypoxia.
正确的蛋白质折叠是新合成的蛋白质转运至特定亚细胞区室、细胞外基质或生物体液的一个重要因素。这一过程受一组特定蛋白质（称为分子伴侣）调控。许多应激条件，如缺氧或葡萄糖剥夺，会减缓折叠过程并导致未折叠/错误折叠的蛋白质在细胞内积累。在这些条件下会诱导分子伴侣产生；其中一些被称为氧调节蛋白（ORP）。这些蛋白与未折叠/错误折叠的蛋白质结合以促进正确组装。ORP 150是本研究的对象。缺氧导致体外培养的几种肿瘤细胞系中ORP 150表达增强。在缺氧条件下生长的HeLa细胞（尽管ORP 150表达强烈）与在常氧条件下培养的细胞相比，显示出更高的凋亡率。此外，用特异性小干扰RNA转染这些细胞抑制ORP 150合成，导致凋亡加剧，这一过程的特异性标志物表明：多聚ADP - 核糖蛋白裂解增强以及Bim蛋白表达增加。我们从研究中得出结论，ORP 150合成增加可保护细胞免受缺氧的促凋亡作用。
