Unité Protéolyse, Croissance et Développement Musculaire, INRA USC-2009, Université Bordeaux 1, Avenue des Facultés, 33405 Talence Cedex, France.
Anticancer Res. 2010 Dec;30(12):5085-9.
Peroxiredoxin IV (Prx IV), a member of the peroxiredoxin family, has been shown to be involved in cell protection against radiation. Peroxiredoxins are also overexpressed and involved in the progression of several tumours. Calpains have been shown to be over-activated in alveolar rhabdomyosarcoma (ARMS). The present study focused on the possible cross-regulations between Prx IV and calpains in ARMS cells. Prx IV abundance was quantified by Western blot analysis in ARMS cells and compared with non-malignant LHCN-M2 cells. Its abundance is quantified in ARMS cells treated or untreated with calpain inhibitors moreover its mRNA expression is also quantified by real-time RT-PCR in these cells. The study showed that Prx IV is overexpressed by five times in ARMS cells when compared to non-malignant myoblasts. Moreover, the inhibition of calpains using chemical inhibitors led to a decrease in Prx IV abundance (64.32 ± 8.25 and 76.79 ± 4.60 for the precursor and secretable forms, respectively, with calpain inhibitor III treatment). It is the first time that a Prx IV calpain-dependent up-regulation is revealed. In summary, calpains may be implied in the tumour phenotype of ARMS cells especially through Prx IV regulation and may, thus, represent a potential therapeutic target to stop progression of ARMS tumour.
过氧化物酶 IV（Prx IV）是过氧化物酶家族的一员，已被证明参与细胞的辐射保护。过氧化物酶也过度表达，并参与多种肿瘤的进展。钙蛋白酶已被证明在肺泡横纹肌肉瘤（ARMS）中过度激活。本研究重点研究了 ARMS 细胞中 Prx IV 和钙蛋白酶之间可能的交叉调控。通过 Western blot 分析在 ARMS 细胞中定量 Prx IV 的丰度，并与非恶性 LHCN-M2 细胞进行比较。此外，还通过实时 RT-PCR 在这些细胞中定量其 mRNA 表达。研究表明，与非恶性成肌细胞相比，ARMS 细胞中 Prx IV 的表达增加了五倍。此外，使用化学抑制剂抑制钙蛋白酶会导致 Prx IV 丰度降低（用钙蛋白酶抑制剂 III 处理时，前体和可分泌形式分别为 64.32 ± 8.25 和 76.79 ± 4.60）。这是首次揭示 Prx IV 依赖钙蛋白酶的上调。总之，钙蛋白酶可能通过 Prx IV 调节参与 ARMS 细胞的肿瘤表型，因此可能成为阻止 ARMS 肿瘤进展的潜在治疗靶点。
