Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
Antioxid Redox Signal. 2012 Feb 1;16(3):245-61. doi: 10.1089/ars.2011.3952. Epub 2011 Oct 21.
Many studies have reported that the generation of reactive oxygen species (ROS) increases during the differentiation of muscle-derived C2C12 cells. Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against oxidative stress. However, the role of Prx-2 in muscle differentiation has not been investigated.
In this study, we demonstrated that Prx-2 expression increases during muscle differentiation and regeneration in response to exogenous H(2)O(2). This increase occurs only in myoblast cell lines because no increase in Prx-2 expression was observed in the NIH3T3, MEF, Chang, or HEK293 cell lines. The antioxidants, N-acetyl L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), both suppressed myogenesis and Prx-2 expression. Moreover, Prx-2 was upregulated at the transcriptional level by NF-κB during the differentiation of muscle-derived C2C12 cells. We also found that inhibition of phosphatidylinositol 3-kinase (PI3K) blocks NF-κB activation and suppresses Prx-2 expression. Interestingly, Prx-2 knockdown increased the expression levels of other antioxidant enzymes, including all of the other Prx family member, thioredoxin-1 (Trx-1) and catalase, but also enhanced the accumulation of endogenous ROS during muscle differentiation.
In this study, we demonstrated for the first time that Prx-2 is unregulated during the muscle differentiation and regeneration.
Prx-2 is upregulated via the PI3K/NF-κB pathway and attenuates oxidative stress during muscle differentiation and regeneration.
许多研究报告指出，在肌源性 C2C12 细胞的分化过程中，活性氧（ROS）的产生增加。过氧化物还原酶-2（Prx-2）是一种丰富的哺乳动物酶，可防止氧化应激。然而，Prx-2 在肌肉分化中的作用尚未得到研究。
在这项研究中，我们证明 Prx-2 的表达在肌肉分化和再生过程中会增加，以应对外源性 H2O2。这种增加仅发生在成肌细胞系中，因为在 NIH3T3、MEF、Chang 或 HEK293 细胞系中未观察到 Prx-2 表达增加。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）和 4,5-二羟基-1,3-苯二磺酸（Tiron）均抑制肌生成和 Prx-2 的表达。此外，在肌肉源性 C2C12 细胞的分化过程中，NF-κB 使 Prx-2 在转录水平上上调。我们还发现，抑制磷脂酰肌醇 3-激酶（PI3K）会阻止 NF-κB 的激活并抑制 Prx-2 的表达。有趣的是，Prx-2 敲低增加了其他抗氧化酶的表达水平，包括所有其他 Prx 家族成员，硫氧还蛋白-1（Trx-1）和过氧化氢酶，但也增强了肌肉分化过程中内源性 ROS 的积累。
在这项研究中，我们首次证明 Prx-2 在肌肉分化和再生过程中被调控。
Prx-2 通过 PI3K/NF-κB 途径上调，并在肌肉分化和再生过程中减轻氧化应激。
