Hypoxia enhances the senescence effect of bortezomib--the proteasome inhibitor--on human skin fibroblasts.
Hypoxia enhances the senescence effect of bortezomib--the proteasome inhibitor--on human skin fibroblasts.
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DOI：
10.1155/2014/196249
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发表时间：
2014
影响因子：
--
通讯作者：
Cechowska-Pasko M
中科院分区：
文献类型：
--
作者：
Krętowski R;Borzym-Kluczyk M;Cechowska-Pasko M
26S 蛋白酶体抑制剂硼替佐米可选择性诱导某些癌细胞凋亡。然而，其选择性的本质仍然未知。这里提出的研究提供了有关硼替佐米对正常成纤维细胞的细胞作用的新信息。我们发现，在含氧量正常的条件下，凋亡细胞的百分比没有显着变化，与孵育时间无关，并检查了硼替佐米的浓度（25nmol/L 或 50nmol/L）。在缺氧条件下，与对照相比，我们没有观察到硼替佐米对孵育 24 小时和 48 小时的成纤维细胞凋亡有任何影响。仅在成纤维细胞在缺氧条件下孵育12小时的情况下，观察到细胞凋亡显着增加，这取决于硼替佐米的浓度。我们的研究表明，硼替佐米会导致正常成纤维细胞（尤其是在缺氧条件下培养的成纤维细胞）的衰老呈时间依赖性增加。此外，我们证明氧调节蛋白150（ORP150）的表达仅在缺氧条件下在成纤维细胞中被诱导，表明该蛋白可能在对环境应激的细胞保护反应中发挥重要作用。
The 26S proteasome inhibitor, bortezomib, selectively induces apoptosis in some cancer cells. However, the nature of its selectivity remains unknown. The study presented here provides novel information on cellular effects of bortezomib in normal fibroblasts. We have found that in normoxic conditions the percent of apoptotic cells did not change significantly, independently on incubation time and examined concentration of bortezomib (25 nmol/L or 50 nmol/L). In hypoxic conditions we did not observe any effect of bortezomib on apoptosis of fibroblasts incubated for 24 h and 48 h in comparison to control. Only in the case of fibroblasts incubated for 12 hours in hypoxia significant increase in apoptosis, dependent on concentration of bortezomib, was observed. Our study has shown that bortezomib causes a time-dependent increase in senescence of normal fibroblasts, especially of these incubated in hypoxic conditions. Moreover, we demonstrated that oxygen regulated protein 150 (ORP150) expression was induced in fibroblasts in hypoxia conditions only, suggesting that this protein may play an important role in the cytoprotective response to environmental stress.
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影响因子：
5.7
作者：
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通讯作者：
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影响因子：
3.1
作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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