The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H₂O₂-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H₂O₂-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.

中文翻译：

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REDD1/TXNIP 复合物通过线粒体途径加速氧化应激诱导的髓核细胞凋亡

髓核（NP）细胞的死亡是椎间盘（IVD）退变的重要原因。由功能失调的线粒体引起的氧化还原障碍被认为是 NP 细胞存活的重要风险。鉴定维持 NP 细胞中线粒体功能的关键蛋白质是有价值的。先前的一项研究发现，在椎间盘退变过程中，发育和 DNA 损伤反应 1 (REDD1) 被上调，REDD1 可导致 NP 细胞凋亡。因此，本研究进一步探讨了REDD1对IVD退化的影响。我们的结果表明REDD1通过线粒体途径促进NP细胞凋亡。重要的是，REDD1 与 TXNIP 形成了一个复合体以加强其自身的作用，并且该组合在 H ₂ O _{2下得到巩固}- 诱导的氧化应激。REDD1/TXNIP复合物的联合抑制在恢复细胞增殖和加速细胞凋亡方面优于单独使用REDD1或TXNIP。此外，p53 作为 REDD1 的转录因子在氧化应激下调节 REDD1/TXNIP 复合物。总之，我们的结果表明REDD1/TXNIP 复合物通过线粒体途径介导H ₂ O ₂诱导的人NP 细胞凋亡和IVD 变性。对这些位点的干扰以实现线粒体氧化还原稳态可能是氧化应激相关的 IVD 变性的一种新的治疗策略。