AMPK-PINK1/Parkin Mediated Mitophagy Is Necessary for Alleviating Oxidative Stress-Induced Intestinal Epithelial Barrier Damage and Mitochondrial Energy Metabolism Dysfunction in IPEC-J2.
AMPK-PINK1/Parkin Mediated Mitophagy Is Necessary for Alleviating Oxidative Stress-Induced Intestinal Epithelial Barrier Damage and Mitochondrial Energy Metabolism Dysfunction in IPEC-J2.
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AMPK-PINK1/Parkin 介导的线粒体自噬对于缓解 IPEC-J2 中氧化应激诱导的肠上皮屏障损伤和线粒体能量代谢障碍是必要的
DOI：
10.3390/antiox10122010
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发表时间：
2021-12-18
期刊：
影响因子：
--
通讯作者：
Hu C
中科院分区：
文献类型：
--
作者：
Cao S;Xiao H;Li X;Zhu J;Gao J;Wang L;Hu C
氧化还原生物和氧化应激的失衡导致肠道屏障损伤和丝裂原吞噬。然而，有丝分裂在氧化应激和肠道功能中的作用仍然存在很大的不确定性。在这里，我们展示了过氧化氢(H_2O_2)诱导的氧化应激对肠上皮细胞氧化平衡、肠屏障功能和线粒体能量代谢的影响及其机制。在本研究中，我们发现过氧化氢诱导的氧化应激激活了一磷酸腺苷激活的蛋白激酶(AMPK)，并增强了猪肠道上皮细胞(IPEC-J2)的有丝分裂。而化合物C(AMPK抑制剂)和MDVI-1(吞噬丝裂酶抑制剂)则显著降低超氧化物歧化酶(SOD)活性，增加线粒体活性氧(ROS)水平。此外，化合物C和MDVI-1显著降低了过氧化氢处理的IPEC-J2的跨上皮电阻值(TER)，增加了异硫氰酸酯-葡聚糖(FD4)的通量。此外，化合物C和mdivi-1显著降低了线粒体复合体II的活性。海马XF96数据显示，化合物C+mdivi-1+H_2O_2处理显著降低了最大呼吸耗氧量和备用呼吸量。此外，化合物C或mdivi-1处理减少了线粒体自噬小体的形成。这些结果揭示了AMPK和PINK1/Parkin介导的有丝分裂对于减轻氧化应激所致的IPEC-J2肠上皮屏障损伤和线粒体能量代谢障碍是必要的。
The imbalance of redox biology and oxidative stress leads to intestinal barrier injury and mitophagy. However, much uncertainty still exists about the role of mitophagy in oxidative stress and intestinal function. Here, we showed the effects of hydrogen peroxide (H2O2)-induced oxidative stress on intestinal epithelial cell oxidation balance, intestinal barrier function and mitochondrial energy metabolism and its underlying mechanism. In this study, we found that H2O2-induced oxidative stress activated adenosine monophosphate-activated protein kinase (AMPK) and enhanced mitophagy in intestinal porcine epithelial cells (IPEC-J2). While compound C (AMPK inhibitor) and mdivi-1 (mitophagy inhibitor) significantly reduced the activity of superoxide dismutase (SOD) and increased mitochondrial reactive oxygen species (ROS) levels in H2O2 treated cells. Moreover, compound C and mdivi-1 significantly reduced the trans-epithelium electrical resistant (TER) and increased the fluorescein isothiocyanate-dextran (FD4) flux in H2O2 treated IPEC-J2. Furthermore, compound C and mdivi-1 significantly reduced the activity of mitochondrial complex II. Seahorse XF96 data showed that compound C + mdivi-1+ H2O2 treatment significantly reduced maximum respiratory oxygen consumption and spare respiratory capacity. Additionally, compound C or mdivi-1 treatment reduced the formation of mitochondrial autophagosomes. These results unveiled that AMPK and PINK1/Parkin mediated mitophagy is necessary for alleviating oxidative stress induced intestinal epithelial barrier damage and mitochondrial energy metabolism dysfunction in IPEC-J2.
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影响因子：
7
作者：
Mao X;Lv M;Yu B;He J;Zheng P;Yu J;Wang Q;Chen D
通讯作者：
Chen D
影响因子：
29
作者：
Mottillo EP;Desjardins EM;Crane JD;Smith BK;Green AE;Ducommun S;Henriksen TI;Rebalka IA;Razi A;Sakamoto K;Scheele C;Kemp BE;Hawke TJ;Ortega J;Granneman JG;Steinberg GR
通讯作者：
Steinberg GR
影响因子：
13.3
作者：
Baechler, Brittany L.;Bloemberg, Darin;Quadrilatero, Joe
通讯作者：
Quadrilatero, Joe
影响因子：
--
作者：
Feng, Junxia;Li, Hongyan;Li, Jingchun
通讯作者：
Li, Jingchun
槲皮素对肠猪肠细胞细胞增殖和H₂O₂诱导的凋亡的影响。
DOI：
10.3390/molecules23082012
发表时间：
2018-08-12
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chen Z;Yuan Q;Xu G;Chen H;Lei H;Su J
通讯作者：
Su J