Activating Nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney.
Activating Nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney.
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DOI：
10.1371/journal.pone.0047299
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yu HJ
中科院分区：
文献类型：
--
作者：
Chung SD;Lai TY;Chien CT;Yu HJ
单侧输尿管梗阻（UUO）肾组织中，氧化应激和炎症反应的加剧可导致细胞程序性死亡，即自噬、凋亡和焦亡。萝卜硫素激活NF-E2相关的核因子红细胞-2（Nrf-2）信号通路可改善UUO诱导的肾损害。在雌性Wistar大鼠的左肾中诱导UUO。检测肾血流量、皮质和髓质氧分压及活性氧（ROS）水平。通过免疫组化和Western印迹法评价UUO肾脏的纤维化、艾德-1（巨噬细胞/单核细胞）浸润、氧化应激、自噬、凋亡和焦亡。研究了萝卜硫素（一种Nrf-2激活剂）对Nrf-2和线粒体应激相关蛋白和肾损伤的影响。UUO使肾血流量和氧分压降低，肾组织ROS、3-硝基酪氨酸染色、艾德-1浸润和纤维化增加。肾小管Beclin-1表达在UUO 4 h开始增强，3d时进一步增强，而Atg-5-Atg 12和LC 3-II表达在3d时增加。UUO后3d，肾组织Bax/Bcl-2比值、caspase 3和PARP片段增加，凋亡形成伴随caspase 1和IL-1β表达增加，导致肾组织细胞凋亡。UUO减少核Nrf-2易位，增加胞质和抑制性Nrf-2表达，增加胞质Bax易位到线粒体，并增强线粒体细胞色素c释放到UUO肾脏的胞质溶胶中。莱菔硫烷显著增加核Nrf-2易位，减少线粒体Bax易位和细胞色素c释放到细胞质中，从而减少肾损伤。总之，萝卜硫素通过激活Nrf-2信号传导保护线粒体功能并抑制UUO诱导的肾氧化应激、炎症、纤维化、自噬、凋亡和焦亡。
Exacerbated oxidative stress and inflammation may induce three types of programmed cell death, autophagy, apoptosis and pyroptosis in unilateral ureteral obstruction (UUO) kidney. Sulforaphane activating NF-E2-related nuclear factor erythroid-2 (Nrf-2) signaling may ameliorate UUO-induced renal damage. UUO was induced in the left kidney of female Wistar rats. The level of renal blood flow, cortical and medullary oxygen tension and reactive oxygen species (ROS) was evaluated. Fibrosis, ED-1 (macrophage/monocyte) infiltration, oxidative stress, autophagy, apoptosis and pyroptosis were evaluated by immunohistochemistry and Western blot in UUO kidneys. Effects of sulforaphane, an Nrf-2 activator, on Nrf-2- and mitochondrial stress-related proteins and renal injury were examined. UUO decreased renal blood flow and oxygen tension and increased renal ROS, 3-nitrotyrosine stain, ED-1 infiltration and fibrosis. Enhanced renal tubular Beclin-1 expression started at 4 h UUO and further enhanced at 3d UUO, whereas increased Atg-5-Atg12 and LC3-II expression were found at 3d UUO. Increased renal Bax/Bcl-2 ratio, caspase 3 and PARP fragments, apoptosis formation associated with increased caspase 1 and IL-1β expression for pyroptosis formation were started from 3d UUO. UUO reduced nuclear Nrf-2 translocation, increased cytosolic and inhibitory Nrf-2 expression, increased cytosolic Bax translocation to mitochondrial and enhanced mitochondrial Cytochrome c release into cytosol of the UUO kidneys. Sulforaphane significantly increased nuclear Nrf-2 translocation and decreased mitochondrial Bax translocation and Cytochrome c release into cytosol resulting in decreased renal injury. In conclusion, sulforaphane via activating Nrf-2 signaling preserved mitochondrial function and suppressed UUO-induced renal oxidative stress, inflammation, fibrosis, autophagy, apoptosis and pyroptosis.
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影响因子：
3
作者：
Haugen, E;Nath, KA
通讯作者：
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影响因子：
4.2
作者：
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影响因子：
7.4
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
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影响因子：
7.7
作者：
Jiang T;Huang Z;Lin Y;Zhang Z;Fang D;Zhang DD
通讯作者：
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影响因子：
3.7
作者：
Kathiria AS;Butcher LD;Feagins LA;Souza RF;Boland CR;Theiss AL
通讯作者：
Theiss AL