Tempol Protects Against Acute Renal Injury by Regulating PI3K/Akt/mTOR and GSK3β Signaling Cascades and Afferent Arteriolar Activity.
Tempol Protects Against Acute Renal Injury by Regulating PI3K/Akt/mTOR and GSK3β Signaling Cascades and Afferent Arteriolar Activity.
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Tempol 通过调节 PI3K/Akt/mTOR 和 GSK3β 信号级联和传入小动脉活动来防止急性肾损伤
DOI：
10.1159/000490338
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发表时间：
2018
影响因子：
2.8
通讯作者：
Lai EY
中科院分区：
文献类型：
--
作者：
Zhang G;Wang Q;Wang W;Yu M;Zhang S;Xu N;Zhou S;Cao X;Fu X;Ma Z;Liu R;Mao J;Lai EY
自由基清除剂tempol是一种抗缺血性损伤的保护性抗氧化剂。肾小管上皮细胞凋亡是肾缺血再灌注损伤的主要变化之一。同时，一些与细胞凋亡和炎症相关的蛋白也参与了肾I/R损伤。我们验证了tempol通过激活蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PKB，Akt/mTOR）和糖原合成酶激酶3β（GSK 3 β）途径以及协调凋亡和炎症相关蛋白来保护肾I/R损伤的假设。将C57 B1/6小鼠的右肾蒂夹闭30分钟，并在研究中移除左肾。采用全自动生化分析仪测定血清生化指标，评价肾损伤程度。用Western blot法检测缺血再灌注小鼠肾脏Akt/mTOR和GSK 3 β通路的表达，并与假手术组比较。检测血尿素氮（BUN）、肌酐（Cr）、超氧阴离子（O2.超氧化物歧化酶（SOD）和过氧化氢酶（CAT）均显著降低。然而，tempol治疗阻止了这些变化。此外，I/R损伤降低了肾脏中p-Akt、p-GSK 3 β、p-mTOR、Bcl 2的表达，增加了肾脏中NF-κB、p-JNK和p53的表达，tempol显着使这些变化正常化。此外，肾I/R损伤降低了传入小动脉对血管紧张素II（Ang II）的反应，而tempol治疗改善了传入小动脉的活动。Tempol减轻肾I/R损伤。其保护机制可能与激活PI 3 K/Akt/mTOR和GSK 3 β通路、抑制细胞损伤标志物和炎症因子以及改善传入小动脉活动有关。
Free radical scavenger tempol is a protective antioxidant against ischemic injury. Tubular epithelial apoptosis is one of the main changes in the renal ischemia/reperfusion (I/R) injury. Meanwhile some proteins related with apoptosis and inflammation are also involved in renal I/R injury. We tested the hypothesis that tempol protects against renal I/R injury by activating protein kinase B/mammalian target of rapamycin (PKB, Akt/mTOR) and glycogen synthase kinase 3β (GSK3β) pathways as well as the coordinating apoptosis and inflammation related proteins. The right renal pedicle of C57Bl/6 mouse was clamped for 30 minutes and the left kidney was removed in the study. The renal injury was assessed with serum parameters by an automatic chemistry analyzer. Renal expressions of Akt/mTOR and GSK3β pathways were measured by western blot in I/R mice treated with saline or tempol (50mg/kg) and compared with sham-operated mice. The levels of blood urea nitrogen (BUN), creatinine and superoxide anion (O2.-) increased, and superoxide dismutase (SOD) and catalase (CAT) decreased significantly after renal I/R injury. However, tempol treatment prevented the changes. Besides, I/R injury reduced renal expression of p-Akt, p-GSK3β, p-mTOR, Bcl2 and increased NF-κB, p-JNK and p53 in kidney, tempol significantly normalized these changes. In addition, renal I/R injury reduced the response of afferent arteriole to Angiotensin II (Ang II), while tempol treatment improved the activity of afferent arteriole. Tempol attenuates renal I/R injury. The protective mechanisms seem to relate with activation of PI3K/Akt/mTOR and GSK3β pathways, inhibition of cellular damage markers and inflammation factors, as well as improvement of afferent arteriolar activity.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1111/apha.12745
发表时间：
2016-10
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Huang Q;Wang Q;Zhang S;Jiang S;Zhao L;Yu L;Hultström M;Patzak A;Li L;Wilcox CS;Lai EY
通讯作者：
Lai EY
影响因子：
15.9
作者：
Melnikov, VY;Faubel, S;Edelstein, CL
通讯作者：
Edelstein, CL
影响因子：
3.5
作者：
Aksu U;Ergin B;Bezemer R;Kandil A;Milstein DM;Demirci-Tansel C;Ince C
通讯作者：
Ince C
影响因子：
8.8
作者：
Bálint E E;Vousden KH
通讯作者：
Vousden KH