The gut epithelial is known as the most critical barrier for protection against harmful antigens and pathogens. Oxidative stress has been implicated in the dysfunction of the intestine barrier. Hence, effective and safe therapeutic approaches for maintaining intestinal redox balance are urgently needed. Curcumin has gained attention for its vast beneficial biological function via antioxidative stress. However, whether the curcumin can relief intestine damage and mitochondrial injury induced by oxidative stress is still unclear. In this study, we found that curcumin can effectively ameliorate hydrogen peroxide (H2O2)-induced oxidative stress, intestinal epithelial barrier injury and mitochondrial damage in porcine intestinal epithelial cells (IPEC-J2 cells) in a PTEN-induced putative kinase (PINK1)-Parkin mitophagy dependent way. Mechanistically, depletion of Parkin (a mitophagy related protein) abolished curcumin's protective action on anti-oxidative stress, improving intestinal barrier and mitochondrial function in porcine intestinal epithelial cells (IPEC-J2) induced by H2O2. Consistently, the protective effect of curcumin was not found in cells transfected with GFP-ParkinΔUBL, which encodes a mutant Parkin protein without the ubiquitin E3 ligase activity, indicating that the ubiquitin E3 ligase of Parkin is required for curcumin's protective effects. On the other hand, we also found that the protective function of curcumin was diminished when PRKAA1 was depleted in IPEC-J2 cells treated with H2O2. Immunofluorescence and luciferase assay showed that curcumin dramatically enhanced nuclear translocation and transcriptional activity of transcription factor EB (TFEB) in IPEC-J2 cells treated with H2O2, and it was ameliorated by co-treated with compound C, an Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, which means curcumin promotes TFEB transcript via AMPK signal pathway. Consistent with in vitro data, dietary curcumin protected intestinal barrier function, improved redox status, alleviated mitochondrial damage, triggered mitophagy and influenced AMPK-TFEB signal pathway in a well-established pig oxidative stress model by challenging with diquat. Taken together, these results unveil that curcumin ameliorates oxidative stress, enhances intestinal barrier function and mitochondrial function via the induction of Parkin dependent mitophagy through AMPK activation and subsequent TFEB nuclear translocation.

中文翻译：

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姜黄素通过通过AMPK-TFEB信号途径促进帕金依赖性线粒体改善了氧化应激诱导的肠屏障损伤和线粒体损伤。

肠道上皮被称为保护有害抗原和病原体的最关键屏障。氧化应激与肠屏障功能障碍有关。因此，迫切需要保持肠道氧化还原平衡的有效和安全的治疗方法。姜黄素因其通过抗氧化应激的广泛有益的生物学功能而受到关注。然而，姜黄素是否能缓解由氧化应激引起的肠道损伤和线粒体损伤尚不清楚。在这项研究中，我们发现姜黄素可以有效缓解PTEN诱导的假定激酶（PINK1）-帕金森依赖的方式。机械上，减少帕金蛋白（一种与线粒体相关的蛋白质）消除了姜黄素对抗氧化应激的保护作用，改善了H2O2诱导的猪肠道上皮细胞（IPEC-J2）的肠屏障和线粒体功能。一致地，在用GFP-ParkinΔUBL转染的细胞中未发现姜黄素的保护作用，该细胞编码无泛素E3连接酶活性的突变型Parkin蛋白，这表明姜黄素的保护作用需要Parkin的泛素E3连接酶。另一方面，我们还发现当过氧化氢处理的IPEC-J2细胞中PRKAA1耗尽时，姜黄素的保护功能减弱。免疫荧光和荧光素酶分析表明，姜黄素显着增强了H2O2处理的IPEC-J2细胞中核转录因子EB（TFEB）的核转运和转录活性，并与化合物C（腺苷5'-单磷酸腺苷（AMP））共同处理得到改善激活蛋白激酶（AMPK）抑制剂，这意味着姜黄素通过AMPK信号途径促进TFEB转录。与体外数据一致，日粮姜黄素可通过敌草快的攻击在成熟的猪氧化应激模型中保护肠屏障功能，改善氧化还原状态，减轻线粒体损伤，触发线粒体并影响AMPK-TFEB信号通路。总而言之，这些结果揭示了姜黄素可改善氧化应激，