Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Int J Mol Sci. 2023 Feb 14;24(4):3851. doi: 10.3390/ijms24043851.
The mechanisms of acute kidney injury and chronic kidney disease remain incompletely revealed, and drug development is a pressing clinical challenge. Oxidative stress-induced cellular senescence and mitochondrial damage are important biological events in a variety of kidney diseases. As a type of carotenoid, β-Cryptoxanthin (BCX) has various biological functions, which means it is a potential therapeutic candidate for the treatment of kidney disease. However, the role of BCX in the kidney is unclear, and the effect of BCX on oxidative stress and cellular senescence in renal cells is also unknown. Therefore, we conducted a series of studies on human renal tubular epithelial (HK-2) cells in vitro. In the present study, we investigated the effect of BCX pretreatment on HO-induced oxidative stress and cellular senescence and explored the potential mechanism of BCX action. The results showed that BCX attenuated HO-induced oxidative stress and cellular senescence in HK-2 cells. Moreover, BCX promoted NRF2 nuclear expression, maintained mitochondrial function, and reduced mitochondrial damage in HK-2 cells. In addition, silencing NRF2 altered the protective effect of BCX on mitochondria and significantly reversed the anti-oxidative stress and anti-senescence effects of BCX in HK-2 cells. We concluded that BCX maintained mitochondrial function by promoting NRF2 nuclear translocation to inhibit oxidative stress-induced senescence in HK-2 cells. In light of these findings, the application of BCX might be a promising strategy for the prevention and treatment of kidney diseases.
急性肾损伤和慢性肾脏病的发病机制仍不完全清楚，药物研发是一项紧迫的临床挑战。氧化应激诱导的细胞衰老和线粒体损伤是多种肾脏疾病的重要生物学事件。β-隐黄质（BCX）作为一种类胡萝卜素，具有多种生物学功能，是治疗肾脏疾病的潜在治疗候选药物。然而，BCX 在肾脏中的作用尚不清楚，BCX 对肾脏细胞氧化应激和细胞衰老的影响也不清楚。因此，我们在体外进行了一系列人肾小管上皮细胞（HK-2 细胞）的研究。在本研究中，我们研究了 BCX 预处理对 HO 诱导的氧化应激和细胞衰老的影响，并探讨了 BCX 作用的潜在机制。结果表明，BCX 可减轻 HO 诱导的 HK-2 细胞氧化应激和细胞衰老。此外，BCX 可促进 NRF2 核表达，维持 HK-2 细胞线粒体功能，减少线粒体损伤。此外，沉默 NRF2 改变了 BCX 对线粒体的保护作用，并显著逆转了 BCX 在 HK-2 细胞中的抗氧化应激和抗衰老作用。我们得出结论，BCX 通过促进 NRF2 核易位来维持线粒体功能，从而抑制 HK-2 细胞中氧化应激诱导的衰老。鉴于这些发现，BCX 的应用可能是预防和治疗肾脏疾病的有前途的策略。
