N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway.
N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway.
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DOI：
10.5483/bmbrep.2015.48.11.112
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发表时间：
2015-11
期刊：
影响因子：
3.8
通讯作者：
Lee JC
中科院分区：
文献类型：
--
作者：
Lee D;Kook SH;Ji H;Lee SA;Choi KC;Lee KY;Lee JC
核因子（红细胞衍生2）样2（Nrf 2）/血红素加氧酶-1（HO-1）通路在氧化应激下骨代谢中的作用存在争议。我们研究了Nrf 2/HO-1通路如何影响MC 3 T3-E1细胞对过氧化氢（H2 O2）、N-乙酰半胱氨酸（NAC）或两者的成骨细胞分化。暴露于H2 O2的细胞碱性磷酸酶活性，钙积累，成骨细胞标志物，如骨钙素和runt相关转录因子-2的表达下降。而H2 O2处理则增加了Nrf 2和HO-1的表达。血红素，一种化学HO-1诱导剂，通过增加HO-1表达和减少成骨标记基因，模拟H2 O2对成骨细胞分化的抑制作用。用NAC预处理恢复了H2 O2诱导的细胞中的所有变化，使其接近正常水平。总的来说，我们的研究结果表明，H2 O2介导的Nrf 2/HO-1通路的激活负调控成骨细胞分化，这是由NAC抑制。[BMB报告2015; 48（11）：636-641]
There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]