Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative injury and calcium oxalate crystal depositions in the rat kidney.
Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative injury and calcium oxalate crystal depositions in the rat kidney.
复制标题
自噬抑制可减轻高草酸尿症引起的肾小管氧化损伤和大鼠肾脏中草酸钙晶体沉积
DOI：
10.1016/j.redox.2018.03.019
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发表时间：
2018-06
期刊：
影响因子：
11.4
通讯作者：
Zeng G
中科院分区：
文献类型：
--
作者：
Duan X;Kong Z;Mai X;Lan Y;Liu Y;Yang Z;Zhao Z;Deng T;Zeng T;Cai C;Li S;Zhong W;Wu W;Zeng G
高血压引起的肾小管上皮细胞氧化损伤是肾草酸钙（CaOx）结石形成的重要因素。自噬已被证明是至关重要的氧化应激诱导的肾小管损伤的调节，但是，很少有人知道它在肾CaOx结石形成的作用。在本研究中，我们发现，自噬拮抗剂氯喹可以显着减弱自噬激活，氧化损伤和线粒体损伤的肾小管细胞在体外和体内，以及高尿酸诱导的CaOx晶体沉积在大鼠肾脏，而自噬激动剂雷帕霉素发挥相反的效果。此外，氯喹预处理可显著减弱磷酸化p38，但雷帕霉素预处理可显著增强磷酸化p38，而p38蛋白激酶激活剂茴香霉素可部分逆转氯喹对大鼠肾小管细胞氧化损伤的保护作用。此外，Beclin1的敲除代表了与氯喹相似的体外对琥珀酸诱导的细胞氧化损伤和p38磷酸化的作用。综上所述，我们的研究结果表明，自噬抑制可以减轻肾小管细胞的氧化损伤和CaOx晶体沉积在大鼠肾脏中通过，至少部分地，抑制p38信号通路的激活，从而代表了自噬在调节肾小管氧化损伤和CaOx晶体沉积的新的作用，第一次。草酸刺激可诱导肾小管上皮细胞自噬激活，并呈时间和剂量依赖性。氯喹介导的自噬抑制减弱了尿酸盐诱导的肾氧化损伤和CaOx晶体沉积。氯喹或Beclin1 siRNA对尿酸诱导的肾小管上皮细胞氧化损伤的保护作用至少部分由p38信号转导介导。
Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects. In addition, oxalate-induced p38 phosphorylation was significantly attenuated by chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment, whereas the protective effect of chloroquine on rat renal tubular cell oxidative injury was partly reversed by a p38 protein kinase activator anisomycin. Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken together, our results revealed that autophagy inhibition could attenuate oxalate-induced oxidative injury of renal tubular cell and CaOx crystal depositions in the rat kidney via, at least in part, inhibiting the activation of p38 signaling pathway, thus representing a novel role of autophagy in the regulation of oxalate-induced renal oxidative injury and CaOx crystal depositions for the first time. Oxalate stimulation could induce autophagy activation in a time- and dose-depended manner in renal tubular epithelial cells. Chloroquine-mediated autophagy inhibition attenuated oxalate-induced renal oxidative injury and CaOx crystal depositions. The protective effect of chloroquine or Beclin1 siRNA on oxalate-induced oxidative injury of renal tubular epithelial cells is mediated, at least in part, by p38 signaling.
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影响因子：
3.1
作者：
Evan AP;Worcester EM;Coe FL;Williams J Jr;Lingeman JE
通讯作者：
Lingeman JE
DOI：
10.1016/j.juro.2015.11.048
发表时间：
2016-04
期刊：
The Journal of urology
影响因子：
--
作者：
Kusmartsev S;Dominguez-Gutierrez PR;Canales BK;Bird VG;Vieweg J;Khan SR
通讯作者：
Khan SR
DOI：
10.1042/bj20111451
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Giordano S;Zhang J
通讯作者：
Zhang J
影响因子：
2.5
作者：
Kim, Wan-Young;Nam, Sun Ah;Kim, Yong Kyun
通讯作者：
Kim, Yong Kyun
DOI：
10.1124/jpet.111.186866
发表时间：
2012-02-01
影响因子：
3.5
作者：
Liu, Wei Jing;Xie, Shu Hua;Park, Tae Sun
通讯作者：
Park, Tae Sun